Pathology of the Paratesticular Region

Chapter
13
Pathology of the Paratesticular Region
HELEN MICHAEL and JOHN R. SRIGLEY
INTRODUCTION
The paratesticular region is a relatively small anatomical
compartment containing a disproportionately large number
of anatomic structures. In addition to the testicular collecting system there are mesothelial and mesenchymal components representing extensions of the abdominal cavity and
retroperitoneum. The epithelial, mesothelial, and connective tissue elements give rise to a wide variety of pathologic
conditions including an interesting array of neoplasms and
tumor-like lesions.
EMBRYOLOGY, ANATOMY, AND HISTOLOGY
Embryology
The embryology of the testis and paratesticular region is
complex and has been the topic of various monographs.1–5
The gonads are first evident as paired mesenchymal ridges
between the dorsal mesentery and the mesonephric ridge
at about 4 weeks’ gestation (Fig. 13-1). The coelomic epithelium that covers these mesenchymal ridges extends into
the underlying mesenchyme to form the primitive sex cords.
Germ cells are first seen in the embryonic yolk sac. They
then migrate along the wall of the hindgut and the dorsal
mesenteric root into the developing gonads by the 6th week
of gestation (Fig. 13-2). The sex cords proliferate under the
influence of the germ cells. Testicular tissue with primitive
seminiferous tubules is detectable by the 7th week of gestation. At about the same time, the primitive tunica albuginea
forms as a layer of flattened cells around the gonad, and the
primitive testis becomes separated from the overlying coelomic epithelium.
In the hilum of the developing testis, the sex cords form
a network of cellular strands that admix with mesonephric
cells from the degenerating mesonephric tubule (Fig. 13-3).
Both sex cords and the mesonephros are thought to contribute to the formation of the rete testis. Hormones from the
embryonic testis are thought to stimulate the mesonephric
duct to develop into the male genital tract collecting system and, at the same time, to suppress development of the
paramesonephric duct. By the end of the 4th month of gestation, the rete cords have merged with the epigenital tubules
of the mesonephros, which form the efferent ductules and
head of the epididymis (Fig. 13-4). The mesonephric duct
develops into the epididymal body and tail and the vas deferens. The caudal portion of the vas deferens joins with the
seminal vesicles, which are also derived from the mesonephric duct. The enlarging testis becomes separated from the
degenerating mesonephros.
The descent of the testis into the scrotum through the
inguinal canal is complex and not totally understood.2 At
the same time that the mesonephros degenerates, a ligament
called a gubernaculum descends from the lower pole of each
gonad along each side of the abdomen, passing through the
abdominal wall at the site of the future inguinal canal, and
it attaches to the scrotal swelling. A peritoneal sac called
the processus vaginalis develops bilaterally, ventral to the
gubernaculum, and herniates through the abdominal wall
along the pathway formed by the gubernaculum. The processus vaginalis carries with it extensions of the abdominal
wall layers, thus forming the wall of the inguinal canal. The
opening formed in the external oblique aponeurosis forms
the superficial inguinal ring, and the defect in the transversalis fascia forms a deep inguinal ring. The external spermatic
fascia is a thin membrane derived from the aponeurosis of
the external oblique muscle at the outer abdominal ring.
The cremasteric fascia originates from the lower border of
the internal oblique muscle. The internal spermatic fascia is
derived from the transversalis fascia.6 These layers become
part of the spermatic cord and the wall of the scrotum.
By about 7 months’ gestation, the testes are located distal
to the deep inguinal ring, a change in position that is attributed to growth of the trunk and pelvis of the embryo.2 The
gubernaculum does not grow after it is formed, and the exact
process of testicular descent into the scrotum is not well
understood. The gubernaculum serves as an anchor that aids
804
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Chapter 13 n Pathology of the Paratesticular Region 805 Excretory mesonephric Glomerulus
tubule
Wolffian
duct
Wolffian duct
Aorta
Dorsal
mesentery
Mesonephric
ridge
A
Genital
ridge
Müllerian
duct
Primitive
sex cords
Proliferating
coelomic
epithelium
B
F i g u r e 1 3 -1 n Embryology of the testis and paratestis. A: At 4 weeks, the genital ridges are apparent as mesenchymal condensations
with a covering of coelomic epithelium that has proliferated. B: At 6 weeks, there is ingrowth of the coelomic epithelium with extension
into the mesenchyme to form the primitive sex cords. (Reprinted from Langman J. Medical Embryology and Human Development—Normal
and Abnormal. 2nd ed. Baltimore, MD: Williams & Wilkins; 1972, Fig. 11-13, with permission.)
in testicular descent, but it does not pull the testis caudally.
Increasing abdominal pressure due to developing organs may
have a role in the process. Androgenic and gonadotrophic
hormones are also thought to be important in the descent of
the testes into the scrotum.2 The testis is positioned posterior
to the processus vaginalis, and it is located in the scrotum by
about the 8th month of gestation. The layers of the inguinal
canal then contract around the spermatic cord.
The vas deferens crosses anterior to the ureter as a result
of the pathway of testicular descent into the scrotum.2,6 The
blood vessels that supply the testis follow a pathway along
the dorsal abdominal wall. The cranial part of the processus vaginalis is obliterated in the perinatal period. The tunica
vaginalis is then an isolated sac lined by mesothelium.
Foregut
Hindgut
Anatomy and Histology
The rete testis, efferent ductules, and epididymis represent a
continuous conduit for seminiferous fluid to be transported
from the seminiferous tubules to the vas deferens.
Rete Testis
The rete testis represents a group of anastomotic channels in the hilum of the testis (Fig. 13-5). These channels
receive the contents of the seminiferous tubules. The rete
also serves as a chamber for mixing the seminiferous tubule
contents, a possible source of seminal fluid, a site of resorption of protein, and the site of a pressure gradient between
the testis and the epididymis.7 There are intratesticular and
Genital ridge
Allantois
Hindgut
Heart
Genital ridge
Primordial
germ cells
Mesonephros
Cloaca
Yolk sac
A
B
F i g u r e 1 3 - 2 n Embryology of the testis and paratestis. A: At 3 weeks, the primordial germ cells form in the wall of the yolk sac.
B: At 6 weeks, the primordial germ cells migrate to the wall of the hindgut, along the dorsal mesenteric root, and into the genital ridges.
(Reprinted from Langman J. Medical Embryology and Human Development—Normal and Abnormal. 2nd ed. Baltimore, MD: Williams &
Wilkins; 1972, Fig. 11-14, with permission.)
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806 Urological Pathology
Degenerating
mesonephric
tubule
Rete testis
cords
Testis
cords
Müllerian
duct
Wolffian
duct
Tunica
albuginea
F i g u r e 1 3 - 3 n Embryology of the testis and paratestis. At 8
weeks of gestation, the tunical albuginea surrounds the developing
testis, and the rete testis cords intermingle with mesonephric tubules
at the hilum. (Reprinted from Langman J. Medical Embryology and
Human Development—Normal and Abnormal. 2nd ed. Baltimore,
MD: Williams & Wilkins; 1972, Fig. 11-15A, with permission.)
extratesticular portions of the rete testis. The tubulae rete are
located in ­testicular interlobular septa, and they connect the
two ends of each seminiferous tubule. They also connect to
the mediastinal rete, which exit the testis as the extratesticular bullae retis. The latter structures anastomose to form the
efferent ductules.
The rete testis is lined by low columnar, cuboidal, or
simple squamous epithelium that rests on basal lamina surrounded by fibroblasts, myoid cells, collagen, and elastin.
These connective tissue components constitute the wall of
F i g u r e 1 3 - 5 n Complex anastomosing channels are present in
the rete testis. The channels are lined by low columnar epithelium.
the rete testis. Microvilli are present on the luminal ­surfaces
of the epithelial cells. Each cell also contains a single
­flagellum that can be seen by electron microscopy.8
Efferent Ductules
Twelve to fifteen efferent ductules connect with the extratesticular rete testis. They make up most of the head of the
epididymis and resorb seminal fluid components. The efferent ductule epithelium is composed of two layers, including columnar epithelial cells and flattened, cuboidal basal
Seminal vesicle
Utriculus
prostaticus
Rete testis
Epigenital
tubules
Testis cords
Tunica
albuginea
Paragenital
tubules
Wolffian or
mesonephric
duct
Appendix
epididymis
Ductus
deferens
Appendix testis
Testis cord
Rete testis
Ductuli
efferentes
Epididymis
Müllerian tubercle
A
Paradidymis
B
F i g u r e 1 3 - 4 n Embryology of the testis and paratestis. A: By 4 months of gestation, the rete ­testis cords have merged with the epigenital tubules of the mesonephros. B: Diagram of the mature ­testis after descent showing the relationships of various structures. (Reprinted
from Langman J. Medical Embryology and Human Development—Normal and Abnormal. 2nd ed. Baltimore, MD: Williams & Wilkins;
1972, Fig. 11-18, with permission.)
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Chapter 13 n Pathology of the Paratesticular Region 807 cells. The luminal surface of the tubules is undulating.
Sometimes, the epithelial cells may display nuclear atypia
and ­cytoplasmic pigment reminiscent of that in the seminal
vesicles.9 The epithelium is surrounded by basement membrane, smooth muscle, and some fibroblasts.8
Epididymis
Most of the head of the epididymis contains the efferent
ductules. The body and tail contain a coiled, 4- to 5-m-long
duct.7,10 The epididymis is involved with sperm storage,
sperm transfer, sperm maturation, and sperm concentration.7
Sperm matures, develops motility, and is stored in the tail
of the epididymis.11 The well-developed smooth muscle wall
surrounding the epididymal tubules assists in transportation
of sperm through the epididymis.
Unlike the wavy luminal surface of the efferent ductules, the epididymal ducts have a smooth luminal contour
(Fig. 13-6). The epididymal epithelium contains tall columnar cells, dark columnar cells, clear cells, and basal cells.
The columnar cells are ciliated, and the cilia decrease in
length from the head to the tail of the organ. The duct lumen
of the tail of the epididymis contains abundant spermatozoa, and clear cells are more prominent in the epithelium
in this area. Periodic acid–Schiff–positive diastase-resistant
intranuclear inclusions are often present in the columnar
cells of the epididymal epithelium,12 most commonly in the
distal portion. Electron-dense, membrane-enclosed bodies
are identified by ultrastructural examination, but no viral
features have been seen.12 Cytoplasmic lipochrome pigment
may also be present. The epididymal epithelium is surrounded by both basement membrane and smooth muscle;
the latter is important for sperm transport. The epithelium
may have a cribriform pattern that should not be mistaken
for hyperplasia.13–15
Vas Deferens (Ductus Deferens)
The tail of the epididymis connects with the vas deferens,
a 30- to 40-cm-long tubular structure that merges with the
seminal vesicle to form the ejaculatory duct.7 The vas deferens epithelium contains pseudostratified columnar epithelial
cells and cuboidal to flattened basal cells. Electron microscopic examination has shown principal cells, peg cells,
mitochondria-rich cells, and basal cells in the epithelium.16
The luminal side of the epithelium is ciliated, and the cilia
become shorter and less abundant as the seminal vesicle is
approached. The epithelium is surrounded by a basement
membrane. In adults, there is a layer of connective tissue
containing elastic fibers between the basement membrane
and the muscular wall of the vas deferens. The muscularis
contains inner and outer longitudinal layers and a middle circular or oblique layer. Like the epididymis, the vas deferens
epithelium may display cribriform architecture, intranuclear
inclusions,12 and lipochrome pigment. The epithelium of the
vas is thrown into folds, and some of these complex infoldings and outpouchings may reach into the muscularis layer.
Testicular Tunics
The tunica albuginea is internal to the tunica vaginalis. It
is composed of thick fibrous tissue that contains smooth
muscle cells and nerve fibers and surrounds the testis except
at the testicular hilus. The myocytes may contract and lead
to an increase in intratesticular pressure. Tumor-like lesions
and rare neoplasms may arise from the tunica albuginea.
The tunica vaginalis is a layer of mesothelium and associated basement membrane that represents the inner lining
of the intrascrotal structures. The visceral tunica vaginalis
forms a serosal lining over the tunica albuginea, covering the testis and most of the epididymal head. It reflects
F i g u r e 1 3 - 6 n Normal epididymis. A: The head of epididymis is composed of efferent ­ductules. They contain pseudostratified epithelium with ciliated cells. The luminal border is undulating. B: Ductus epididymis. Cilia are prominent, and the pseudostratified lining cells
have a smooth luminal border. Smooth muscle surrounds the duct.
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808 Urological Pathology
back on itself superiorly and posteriorly at the mediastinum
testis to become the parietal tunica vaginalis. Urothelial
metaplasia may occur in the tunica vaginalis,17 with formation of von Brunn nest–like structures.8 Squamous
­metaplasia may also occur, and after cystic transformation,
it may account for some epidermoid cysts in the testis and
paratestis.18,19
While the cranial part of the tunica vaginalis normally
becomes obliterated in the perinatal period, sometimes residual mesothelium present in the spermatic cord may result in
cysts or other lesions of mesothelial origin.
The spermatic cord nerves include the genital branch of
the genitofemoral nerve, which innervates the cremasteric
muscle and sends branches to the scrotal skin.6 The testicular
plexus of sympathetic nerve fibers is derived from branches
of renal and aortic nerve plexuses with contributions from
the superior and inferior hypogastric plexuses. These nerves
travel with the testicular artery as well as give off branches to
the epididymis and the vas deferens. Nerves from the pelvic
plexus may accompany the artery of the vas deferens.8
Spermatic Cord
Rete Testis
During its descent into the scrotum, the testis brings with it
the elements of the spermatic cord, including the vas deferens, blood vessels, and nerves.1,2,4,5 The cord is covered
by the spermatic and cremasteric fascia that accompany
the processus vaginalis through the abdominal wall into the
inguinal canal.2,6 The cremasteric muscle is composed of
skeletal muscle bundles present along the outer part of the
spermatic cord and in the wall of the scrotal sac. The loose
connective tissue matrix of the spermatic cord contains scattered bundles of smooth muscle.
The arteries present in the spermatic cord supply blood
to the testis and paratesticular structures. They include the
testicular (spermatic) artery, the artery of the vas deferens,
and the cremasteric artery.6 The testicular artery originates
from the aorta inferior to the renal artery and penetrates the
tunica albuginea to provide the main blood supply to the testis and the epididymis. The anterior and posterior epididymal arteries arise from the testicular artery and supply the
head of the epididymis and the epididymal body and tail,
respectively. The artery of the vas deferens is a branch of
the superior vesicle artery that accompanies the vas deferens
and anastomoses with the main testicular artery or the posterior epididymal artery. The cremasteric artery is a branch of
the deep epigastric artery. It supplies the cremasteric muscle
and other coverings of the spermatic cord. It anastomoses
with branches of the testicular artery.
The epididymal veins anastomose with the testicular
veins6 to form the pampiniform plexus that invests the testicular artery.8 Further venous anastomoses eventually lead
to the right and left testicular veins. The right testicular vein
opens into the inferior vena cava at an acute angle, whereas
the left testicular vein drains into the left renal vein at a right
angle. Increased hydrostatic pressure from the perpendicular
venous anastomosis on the left side is thought to account for
the greater incidence of varicoceles on that side.
The lymphatic channels of the testis and epididymis arise
from a superficial plexus beneath the tunica vaginalis and
a deep plexus in the testis and epididymis.6 These vessels
anastomose into four to eight larger channels that accompany the main testicular blood vessels through the spermatic
cord to drain into the lateral paraaortic and preaortic lymph
node groups.8
The term “dysgenesis of the rete testis” refers to the
­underdeveloped rete testis associated with cryptorchidism20
(Table 13-1).
Testicular abnormalities reported in cryptorchidism
include Sertoli cell–only syndrome (23 cases), diffuse tubular hyalinization (8 cases), mixed tubular atrophy (3 cases),
and maturation arrest of spermatogonia (4 cases).20
The rete has been described as diffusely hypoplastic in
37.5%, hypoplastic and cystic in 50%, and hyperplastic in
12.5% of 40 cryptorchid testes.20 The latter pattern is identical to the lesion described as (idiopathic) rete testis hyperplasia, characterized by tubular, papillary, and cribriform
intratubular epithelial proliferations. Cystic change in the
rete testis associated with cryptorchidism is manifested by
dilated epithelial structures measuring up to 500 µm lined
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Congenital Abnormalities and Ectopia
Table 13-1 n CONGENITAL ABNORMALITIES
AND ASSOCIATED CONDITIONS
Type
Rete testis
Dysgenesis
Cystic dysplasia
Epididymis
Anomalies of
attachment to testis
Cysts
Agenesis
Vas deferens
Congenital absence
Ectopic
Splenic–gonadal fusion
(continuous form)
Ectopic adrenal tissue
Ectopic renal tissue
Associated Conditions
Cryptorchid testis, epididymal
abnormalities
Renal agenesis or cystic dysplasia
of kidney
Von Hippel-Lindau syndrome
In utero DES exposure
Absence of vas deferens and
renal anomalies
Cystic fibrosis
Absent epididymis
Renal anomalies
Imperforate anus, hypospadias
Peromelia, micrognathia,
gastrointestinal abnormalities
TTAGS
Nelson syndrome in some
Undescended testis; rarely
associated with extrarenal
Wilms’ tumor
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Chapter 13 n Pathology of the Paratesticular Region 809 by large cuboidal epithelial cells. The epithelium stains for
both cytokeratin and vimentin in the same manner as the
normal rete epithelium. Some cases have been associated
with efferent duct atrophy, with small duct diameters and
more space than usual between the ducts. Other associated findings included epididymal duct ectasia (21 cases),
an underdeveloped muscular layer in the epididymis
(11 cases), and fat and dilated veins in the mediastinum
testis (3 cases each).
Cryptorchidism is also associated with anomalies of
mesonephric structures, including luminal dilation of the
spermatic duct system, immature muscle layers, and malformations of the epididymis. These multiple abnormalities
associated with cryptorchidism suggest a primary developmental disorder of the mesonephros.21
Epididymis
Congenital anomalies of the epididymis include anomalies
of the attachment to the testes, epididymal cysts, agenesis or
accessory epididymis, ectopic epididymis, and duplication
of the epididymis.
Anomalies of fusion, with detachment of the head of the
epididymis from the testis, and anomalies of suspension have
been reported in children who have had surgery for cryptorchidism.22–24 Fusion anomalies are more commonly associated with abdominal testes, and suspension anomalies are
more often seen when the cryptorchid testis is located more
distally. Some epididymal anomalies are associated with an
absent testis. Anomalies of attachment of the epididymis to
the testis include attachment of the caput and cauda with a
detached corpus, attachment of the epididymal head only,
attachment of the cauda only, and complete separation of the
testes and epididymis.23 Epididymal anomalies may also be
seen in about one-third of boys with hernias and hydroceles
without cryptorchidism, especially if there is a patent processus vaginalis. Detachment of the head of the epididymis
bilaterally results in infertility.
Epididymal cysts are usually asymptomatic lesions that
are discovered incidentally on physical examination or ultrasound. Epididymal cysts may be acquired, but some authors
believe that they have a congenital basis,25 perhaps related to
maturation of the mesonephric ductal system. They are seen
in patients with von Hippel-Lindau syndrome and in some
patients exposed to diethylstilbestrol in utero26 (Table 13-1).
The cysts may represent efferent ducts that did not fuse with
the mesonephric duct during embryogenesis.
Epididymal agenesis is almost always associated with unilateral or bilateral absence of the vas deferens (Table 13-1).
The epididymal head is usually present because it is composed of efferent ducts derived from the genital ridge,
whereas the epididymal body and tail are of mesonephric
derivation.25 A high frequency of renal anomalies is present
in these patients.
Aberrant epididymal tissue is rare. It may be associated with
an undescended testis. One case of ectopic epididymal tissue
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in the appendix testis has been reported.27 Ectopic e­ pididymal
tissue has also been associated with an inguinal hermia sac.28
Epididymal duplication is rare. It is characterized by a
small accessory epididymis branching from the main epididymis. These patients are asymptomatic, and the lesions
are discovered incidentally.
Vas Deferens
Congenital bilateral absence of the vas deferens is a wellstudied abnormality of the wolffian ducts that represents
a primary genital form of cystic fibrosis29 (Table 13-1).
Mutations in the cystic fibrosis transmembrane conductance
gene are associated with wolffian duct abnormalities, including unilateral and bilateral congenital absence of the vas deferens and idiopathic epididymal obstruction.29 The body and
tail of the epididymis are also often absent, so the epididymal head may be prominent and distended with sperm. In
some cases, there may be complete absence of the epididymis. Renal anomalies may be present due to the associated
embryologic origins of these structures.25
Unilateral absence of the vas deferens occurs in <1%
of healthy men. It represents the most frequent congenital anomaly of the vas deferens and involves the left side
more often than the right side.25 It is often detected at the
time of vasectomy. It is not a common cause of infertility if
the contralateral vas is normal. The epididymis associated
with the absent vas may be of variable length. Ipsilateral
renal agenesis may be associated with this condition
(Table 13-1).
Only a few cases of duplicated vas deferens have been
reported.25 This term is restricted to cases where a second
vas deferens is identified within the spermatic cord. The condition needs to be recognized at the time of vasectomy.
Ectopic vas deferens (persisting mesonephric duct) is a
condition wherein the ureter enters the vas deferens.25 A triad
of ectopic vas deferens, imperforate anus, and hypospadias
has been described30 (Table 13-1); it has been present in
about one-fourth of patients with ectopic vas deferens. The
diagnosis of persisting mesonephric duct should be considered in male children with imperforate anus and recurring
urinary tract infections.
One case of a large diverticulum of the vas deferens has
been reported.31 A thickened scrotal vas deferens and azoospermia were present. Another rare congenital anomaly is
crossed dystopia of the vas deferens, a condition in which
the vas deferens crosses the midline and communicates with
the contralateral seminal vesicles.31 Infertility is not associated with that lesion unless additional abnormalities are
present. The diagnosis is made by vasography. Segmental
aplasia of the vas deferens (skip vas) may be unilateral or
bilateral; bilateral lesions result in infertility. Segments of
vas deferens may also be hypoplastic. These conditions represent abnormal mesonephric duct development and may be
associated with abnormalities of the epididymis and seminal vesicles.
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810 Urological Pathology
Ectopic Splenic Tissue and Splenic–Gonadal
Fusion
Splenic and gonadal tissue may fuse during embryogenesis.32 The left gonad is most frequently involved.33 There is
a continuous form of this lesion in which a cord connects
the spleen to the testis; many of those patients have marked
defects of the extremities (peromelia), as well as micrognathia and gastrointestinal abnormalities (Table 13-1). Those
patients may have a scrotal or inguinal mass that becomes
apparent during an inguinal hernia operation or during surgery for an undescended testis. Small aggregates of splenic
tissue may be found in the spermatic cord, or the cord may
be composed entirely of splenic tissue.34
The discontinuous form of splenic–gonadal fusion is
manifested by accessory splenic tissue in the paratestis
region rather than continuity between the spleen and testis.
Accessory splenic tissue has been reported in the epididymis, in the spermatic cord, and between the scrotal skin and
the spermatic cord.33 The splenic tissue has the gross and
microscopic characteristics of normal spleen.
Ectopic Adrenal Tissue
Ectopic adrenal cortical tissue is seen in the paratestis of
1.6% to 15% of male patients.35,36 It typically appears as
­yellow-orange nodules in the spermatic cord, epididymis,
rete testis, tunica albuginea, and between the epididymis and
the testis. It is most often seen in infants, but it may occur in
adults. Nodules of ectopic adrenal tissue may measure 2 to
6 mm in diameter.37 They display three well-defined layers
of adrenal cortex. The zona fasciculata is the predominant
tissue. Adrenal medulla is not present in ectopic adrenal tissue. The characteristic zonation seen in the adrenal cortex is
an important factor in distinguishing ectopic adrenal tissue
from other steroid cell proliferations in this region.
Ectopic adrenal cortex may be the source for neoplasms
such as the testicular tumor of the adrenal genital syndrome (TTAGS) that may be seen in the spermatic cord.38
Similar tumors are seen in patients with Nelson syndrome39
(Table 13-1). These lesions actually represent reversible
hyperplasia of steroid-producing cells in response to high
circulating levels of ACTH.40 Reduction of the ACTH levels
causes regression of the lesion. TTAGS displays nests of cells
with eosinophilic cytoplasm; the cell nests are separated by
fibrous stoma. Intracytoplasmic lipofuscin may be present.
Some authors have suggested that TTAGS arise from pluripotential cells in the testicular hilus rather than adrenal rests.38
mesenchyme. An additional patient had h­ eterotopic renal
tissue that was discovered in association with an intrascrotal Wilms tumor44 (Table 13-1). The renal heterotopia consisted of renal tubules and immature glomeruli that may
have arisen from caudal mesonephric elements present in
the paratesticular area. Primary extrarenal nephrogenic rests
occur rarely in the paratesticular region.45 They display blastema and immature glomeruli and tubules.
Extraparenchymal Leydig Cells
Clusters of Leydig cells are often present in the paratesticular region (Fig. 13-7). They have been reported in the
tunica albuginea and rete testis,46,47 the adventitial tissue
between the tunica albuginea and epididymis, the epididymis, the vas deferens, and the spermatic cord.36,48 A recent
study found Leydig cells outside the testis in 90 of 97 orchiectomy specimens reviewed.49 The testicular tunics were
involved in 50% of cases, and 14.4% of spermatic cords
contained Leydig cells. These cells were associated with
nerves in 25.5% of cases and with vascular spaces in 7.8%
of orchiectomy specimens, but some aggregates of Leydig
cells were not associated with either nerves or blood vessels.49 Leydig cells sometimes contain lipochrome pigment,
Reinke crystals, and multiple nuclei.47 Large aggregates
of extratesticular Leydig cells may be misinterpreted as a
primary paratesticular Leydig cell neoplasm, spread from a
testicular Leydig cell tumor or other rare neoplasms or metastatic disease. Extratesticular Leydig cells may form small
nodules, but the location along nerves and vessels combined with the lack of an expansile paratesticular mass or
testicular neoplasm distinguishes testicular adnexal Leydig
cells from Leydig cell tumor of paratesticular or testis
origin. In contrast to metastatic deposits, no atypia, mitosis,
or stromal reaction is associated with extratesticular Leydig
cell aggregate.
Ectopic Renal Tissue
Ectopic renal tissue in the paratesticular region is rare and
usually occurs in association with an undescended testis.41–43
One case occurred in a 36-year-old man with a painful inguinal swelling.41 An undescended testis was present with an
adjacent ectopic kidney that measured 3 cm in diameter and
contained renal cortex and medulla as well as some immature
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F i g u r e 1 3 - 7 n Perineural Leydig cells. Leydig cells have
abundant eosinophilic cytoplasm and are often associated with
nerve bundles in the paratesticular region.
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Chapter 13 n Pathology of the Paratesticular Region 811 Remnants of Wolffian and Müllerian Ducts
Remnants of the embryonic müllerian and wolffian ducts
give rise to the appendix testis and the appendix epididymis,
respectively. These structures may be subject to various pathologic processes, including cysts, infarcts, and tumors. Cysts
usually occur in the retroperitoneum, mesentery, pelvis, or
paratesticular region. However, one cyst thought to be derived
from a wolffian duct remnant occurred in the liver of an infant
boy. It was connected by a stalk to the head of the epididymis
adjacent to his right abdominal undescended testis.50
Appendix Testis
The appendix testis is a remnant of the paramesonephric
(müllerian) duct that is usually found on the anterosuperior
aspect of the testis in the groove between the testis and the
head of the epididymis.5,7 It is most commonly attached to
the tunica vaginalis of the testis, but it may also be attached
to the epididymis. The appendix testis can be identified in
80% to 90% of men, and it has been found bilaterally in 60%
of patients.7 A thickened area of the tunica vaginalis or focal
calcification may be the only evidence of this structure in
some men. However, it is generally an ovoid structure that
measures 0.5 to 2.5 cm in length.51 It is covered by cuboidal to columnar epithelium that may be stratified (Fig. 13-8).
The connective tissue core contains blood vessels and,
sometimes, smooth muscle cells. Stroma resembling ovarian stroma may also be present. Torsion and infarction of
the appendix testis is usually seen in children or adolescents,
and it is associated with scrotal pain52 that may be mistaken
for processes involving other intrascrotal areas. Chronic torsion may cause detachment of the appendix testis.
Appendix Epididymis
The appendix epididymis is derived from the cranial aspect
of the mesonephric (wolffian) duct. It is identifiable in
only about 25% of specimens.53 It is a cystic structure that
may contain eosinophilic fluid and is lined by cuboidal to
­columnar epithelium. The epithelium is surrounded by a
basement membrane, with a small amount of connective tissue and mesothelial cells on the external aspect. The appendix epididymis may be pedunculated, or it may be adherent
to the head of the epididymis. It may be involved by torsion
and infarction causing scrotal pain, and sometimes it may
become enlarged and suggest a mass lesion.
Aberrant Ductules and Paradidymis
The superior and inferior aberrant ductules (organ of Haller)
and paradidymis (organ of Giraldes) are mesonephric duct
(wolffian) remnants.8 They are near the head or body of the
epididymis in the case of the superior aberrant ductule or the
junction of the tail of the epididymis and the vas deferens
in the case of the inferior aberrant ductule.7 Both are small
tubules or cysts with low columnar epithelium surrounded
by smooth muscle. They may be the source of some epididymal cysts, although epididymal cysts are also encountered in
patients with the von Hippel-Lindau syndrome and in some
patients who were exposed to diethyl-stilbestrol in utero.7,26,54
The paradidymis is usually located adjacent to the vas
deferens in the area of the head of the epididymis. It is a
small tubular structure similar to the aberrant ductules, and
it may result in a spermatic cord cyst.28 It is important not
to mistake the paradidymis for vas deferens in inguinal hernia specimens.55 The well-developed, three-layered muscular
wall of the vas deferens aids in the distinction.
Hernia Sac Inclusions
Hernia sacs from young boys contain glandular or ductal
structures in 1.5% to 6% of cases55–57 (Box 13-1). These
embryonal rests must be distinguished from transected vas
deferens and epididymal tissue because gland inclusions do
not affect reproductive function.
The three types of embryonal rests seen in inguinal hernia sacs include vas deferens–like, epididymis-like and
müllerian-like inclusions.56 The diameter of the remnants,
Box 13-1 l GLANDULAR INCLUSIONS IN
INGUINAL HERNIA SACS
Type of Inclusion
Diagnostic Features
Vas deferens–like
CD10 negative, smooth
muscle actin positive,
­diameter ≤0.8 mm
7/13 CD10 positive, others
negative
CD10 negative
Epididymis-like
Müllerian-like
Normal Anatomic Structures
Normal vas deferens
F i g u r e 1 3 - 8 n Appendix testis. The oblong structure has a
fibrovascular core and is covered by columnar cells.
Amin9780781782814_ch13.indd 811
Normal epididymis
At least focal CD10 positive,
smooth muscle actin positive, diameter ≥1 mm
At least focal CD10 positive
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812 Urological Pathology
correlated with patient age, may aid in distinguishing them
from normal vas deferens.56 Trichrome and immunohistochemical stains for smooth muscle actin are useful because
they distinguish periglandular mesenchymal condensations
in the inclusions from the subepithelial muscle layer seen
in the vas deferens and epididymis. Vas deferens–like and
müllerian-like inclusions do not display the luminal CD10
staining that is seen in normal vas deferens. Two types of
epididymis-like inclusions have been reported.56 One group
displays luminal decoration by CD10 and may represent
aberrant wolffian ductules. The other group does not stain
with this antibody and may represent müllerian remnants.
Congenital Hydrocele
Congenital hydroceles result from a persistent communication
between the tunica vaginalis and the peritoneal cavity. This
communication is normally obliterated after descent of the
testis into the scrotum and usually before the age of 2 years.
Cystic Dysplasia
Cystic testicular dysplasia is rare, and it is an entity seen
in infants and young children.58 It is usually a unilateral
lesion that is associated with an ipsilateral urogenital lesion
such as renal agenesis or cystic dysplasia of the kidney59
(Table 13-1). The lesion is usually manifested by painless testicular enlargement, although one recently reported
patient complained of scrotal pain.60 Involvement of the rete
may be segmental or diffuse. The rete testis in patients with
this disorder displays cystically dilated channels (Fig. 13-9)
that maintain the normal branching pattern of the rete and
do not display epithelial proliferation.21 The rete spaces are
lined by cuboidal to flattened epithelial cells that are surrounded by fibrous stroma. The cysts range in size from 1
to 5 mm in diameter and are visible on gross examination.
Seminiferous tubules are normal. Cystic dysplasia of the rete
testis does not appear to be caused by obstruction of the duct
system, which causes extensive dilation of the rete channels
F i g u r e 1 3 - 9 n Cystic dysplasia. This gross photograph
d­ isplays distorted rete testis architecture due to multilocular cystic
dilation of the rete channels.
Amin9780781782814_ch13.indd 812
as well as dilation of seminiferous tubules in young children.
It is more likely related to an embryologic defect. During
embryogenesis, the rete testis is formed from sex cord stromal tissue; the connection with epididymis (of wolffian duct
origin) may be defective in this disorder, leading to dilated,
blind-ended rete channels.21 Abnormal sodium metabolism
has also been proposed as a cause for this disorder.26 Cystic
dysplasia has also been reported in the epididymis.61
Inflammation and Infection
Inflammatory conditions of infectious or noninfectious origin
may principally affect epididymis, tumor, or spermatic cord or
may involve more than one of those structures. Furthermore,
paratesticular inflammation may be secondary to orchitis. In
this section the entities are discussed under headers of nonspecific and granulomatous inflammation, realizing that both
may have active (acute) and chronic components. Diverse
etiologic agents are associated with these conditions, and in
some instances no identifiable agent is found.
Nonspecific Acute and Chronic Inflammations
Epididymitis represents the most common intrascrotal inflammation.62,63 Chronic infection and inflammation are associated with reactive changes and fibrosis that may simulate a
neoplasm. Acute epididymitis is the most common cause of
an acutely painful scrotum. Bacterial infection may be caused
by a variety of organisms. It is often associated with anatomic
abnormalities, and it is the most common type of epididymitis seen in older men.34 Sexually transmitted Chlamydia
trachomatis or Neisseria gonorrhoeae epididymitis represent
the most common cause of acute scrotal swelling in men
under the age of 35 years.34 Sexually transmitted epididymitis is associated with underlying urologic abnormalities.64
Chlamydia trachomatis epididymitis is minimally destructive,
with periductal and intraepithelial inflammation, epithelial
proliferation, and, sometimes, squamous metaplasia.65 On the
other hand, pyogenic infections such as N. gonorrhoeae are
associated with destructive abscess formation and may create
masses that mimic neoplasia. Low-risk and high-risk types
of human papillomavirus have been detected in epididymal
and ductus deferens tissue from some patients with epididymitis, although neither koilocytotic atypia nor dysplasia was
identified.66 The male urogenital tract may therefore serve as a
reservoir of HPV infection. Older men who develop bacterial
epididymitis are more often infected with Escherichia coli.
Whereas epididymitis is rare in childhood, an increasing
frequency has been reported in children admitted with the
diagnosis of acute scrotum.67 In some cases, E. coli has been
cultured from children with epididymo-orchitis who had no
underlying urinary tract abnormalities.68
Chemical epididymitis occurs when sterile urine refluxes
into the vas deferens, sometimes after heavy lifting or
blunt abdominal trauma that increases the intra-abdominal
pressure.69 The vas deferens and the tail of the epididymis
become inflamed, but no organisms are identified.
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Chapter 13 n Pathology of the Paratesticular Region 813 Schistosomal funiculitis has been reported in a patient
with chronic schistosomal infection of long duration.70
Dirofilaria conjunctivae infection has been seen in the spermatic cord, where it has simulated a neoplasm.71
Granulomatous Inflammation
The most common cause of granulomatous epididymitis is
tuberculosis (Fig. 13-10). The incidence of this disease has
increased because of human immunodeficiency virus infection and intravesical bacille Calmette-Guerin therapy for
superficial bladder tumors.72 There is an association between
renal and genital tuberculosis, with frequent involvement of
the epididymis.73 Painful or painless scrotal enlargement is a
common presenting symptom. Epididymal tuberculosis may
present as a mass lesion in patients that have widespread disease. Secondary hydroceles may be associated with epididymal tuberculosis. Extensive infection can result in sinuses
that communicate with the scrotum.72
Gross examination of tuberculous epididymitis reveals
multiple small white to yellow nodules that typically contain
caseous necrosis. Microscopic examination displays necrotizing granulomatous inflammation with palisading histiocytes and Langhans giant cells. Granulomas originate in the
epididymal stroma and then enlarge, become confluent, and
spread to and secondarily involve the tubules.74
Brucella75,76 and blastomycosis77 have also been implicated in granulomatous epididymitis clinically simulating
neoplasia. Some cases of granulomatous epididymitis have
F i g u r e 1 3 -1 0 n Tuberculous epididymitis. This gross photograph shows partially necrotic tumor-like lesion involving
­epididymis and paratesticular soft tissue.
Amin9780781782814_ch13.indd 813
not been associated with any detectable infectious agent.78
One such case occurred in a 41-year-old man who presented
with a scrotal mass and had a 2.3-cm firm lesion in the tail
of the epididymis.34 Epididymal tubules had necrotic walls,
and there was a significant histiocytic infiltrate associated
with squamous metaplasia.34 No necrosis or Langhans-type
giant cells were seen, and no organisms could be identified
on special stains.
Granulomatous epididymitis may also be caused by fungal organisms. However, fungal epididymitis is very rare and
usually associated with orchitis. Demonstration of the organisms with special histologic stains or culture is necessary if
this diagnosis is a consideration.
Some cases of granulomatous epididymitis with no
apparent infectious agent may have an ischemic etiology.79
In cases thought to be ischemic, granulomatous lesions
display predominantly histiocytic infiltrates and typically
involve tubular walls rather than the epididymal stroma.79
Areas of necrosis and squamous metaplasia may be present.
Ischemic lesions are more frequently located in the head of
the epididymis, where the blood supply is more easily compromised than in the body and tail.34 The vascular supply
for the head of the epididymis consists of only the superior
epididymal artery. The vascular supply for the body and tail
of the epididymis includes numerous anastomoses between
the inferior epididymal and vas deferens arteries, thereby
protecting these areas against ischemia.
Xanthogranulomatous epididymitis is associated with
Gram-negative bacteria and usually requires surgical excision.34,80 These lesions display prominent aggregates of
foamy histiocytes in addition to plasma cells, lymphocytes,
and neutrophils. One reported case80 was bilateral and so
severe that it was difficult to distinguish the epididymis from
the adjacent testis. Xanthogranulomatous funiculitis and
epididymitis have been described in a quadriplegic patient
with unsuccessful voiding.81 Other rare cases of xanthogranulomatous funiculitis have been reported.82 The lesion
presents with spermatic cord enlargement, and the histologic features are identical to those of xanthogranulomatous
epididymitis.
Sarcoidosis
Genitourinary involvement by sarcoidosis is very uncommon. The average age at onset of genital sarcoidosis is 33
years (range 2 to 67).83 Epididymal sarcoidosis has been
reported mainly in black men, some of whom also had
testicular sarcoidosis.84 The spermatic cord may also be
involved. These lesions are often asymptomatic and unilateral, although they may be bilateral.85,86 Firm nodules may
replace the entire epididymis. Nonnecrotizing granulomas
may cause nodules that measure up to 2.5 cm in diameter
and mimic a tumor.84,87,88 Special stains for acid-fast bacilli
and fungi show no organisms. Diffuse involvement of the
epididymis may also be present. Most patients have hilar
adenopathy or reticulonodular lung infiltrates on chest
radiographs. However, genitourinary sarcoidosis has been
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814 Urological Pathology
reported in the absence of radiographically detectable lung
or mediastinal disease.83
Sclerosing Lipogranuloma
Injection of lipids to increase the size of the genitalia has
resulted in granulomatous lesions in the scrotum, the spermatic cord, or the epididymis.89,90 Some have presented as
mass lesions requiring surgical excision.91,92 Most cases have
been associated with a history of exogenous lipid injection
or a history of trauma, but some may have been idiopathic.93
Most patients have presented with localized masses measuring from a few to several centimeters in size.5
Gross examination of resected sclerosing lipogranulomas
reveals fragmented or intact specimens that are gray to yellow and solid or solid with small cysts on gross examination.5 Microscopic examination displays patchy fibrous tissue
containing empty vacuoles of varying size without epithelial
lining cells. Foreign body giant cells may be present. Areas
of hyalinization may be seen, and inflammatory cells include
histiocytes, lymphocytes, plasma cells, and eosinophils. This
lesion is typically patchy in the involved area of the epididymis or spermatic cord. The differential diagnosis of sclerosing
lipogranuloma in the epididymis includes adenomatoid tumor,
sclerosing lipogranuloma, and signet ring carcinoma. None of
those neoplasms contains the empty vacuoles devoid of lining cells that are characteristic of sclerosing lipogranuloma.
Mesothelial-lined tubular structures typical of adenomatoid
tumor are not seen in sclerosing lipogranulomas. Sclerosing
liposarcoma displays atypical nuclei and rare lipoblasts in
fibrous tissue alternating with “lipoma-like” areas. Neither
atypical nuclei nor lipoblasts are seen in sclerosing lipogranuloma. Signet ring carcinomas contain mucinous cytoplasmic
vacuoles that are not present in sclerosing lipogranuloma.
Other Rare Granulomas
Granulomas of paratesticular structures have been reported
due to powder from surgical gloves.94 This was the etiology
in the case of a 2-cm hard mass in the head of the epididymis
and tunica albuginea in one patient.94 Microscopic examination of the mass showed fibrous tissue and epithelioid histiocytes intermingled with foreign body–type giant cells that
contained crystalline material. Radiopaque contrast dye containing lipid has also been reported as a cause of granulomas
of the vas deferens in a 35-year-old infertile man who underwent vesiculoepididymography.95 Partial resection of the vas
deferens revealed a small nodule that showed acute, chronic,
and granulomatous inflammation on microscopic examination. The granulomas contained refractile foreign material.
Cholesterol granulomas (also called cholesteatoma) of
the tunica vaginalis simulating neoplasm have also been
reported.96,97 One such lesion was described in a 52-year-old
man who had a 7-cm mass that had been present since an episode of trauma 25 years earlier.97 Excision of the mass showed
thickening of the tunica vaginalis. Microscopic examination
showed granulomas and fibrosis with foreign body–type
giant cells containing cytoplasmic cholesterol clefts.
Amin9780781782814_ch13.indd 814
Malakoplakia
About one-third of reported cases of testicular and paratesticular malakoplakia involve the epididymis. The testis is usually
involved also,98,99 although sometimes only the epididymis
is affected.100 Rare cases of epididymal malakoplakia present as masses in patients with remote histories of vasectomy
or associated with a hydrocele, and they have occasionally
required surgical excision.101 Other examples of this lesion
have been detected incidentally in orchiectomy specimens
from men with prostate cancer.100 Some patients have histories of urinary tract infections, especially with E. coli. On
microscopic examination, malakoplakia displays aggregates
of histiocytes and inflammatory cells with the characteristic targetoid Michaelis-Gutmann bodies. The inflammatory
infiltrate may overshadow the population of histiocytes in
some cases. Stains for iron (Prussian blue), calcium (von
Kossa), and the periodic acid–Schiff stain may help identify
these structures if they are not seen on routine H&E stains.
Meconium Periorchitis (Also Called Meconium
Vaginalitis)
This lesion usually becomes evident in infants <1 month of
age. Rare infants with this condition have had cystic fibrosis.102 However, several cases have been reported in black
infants, a group that is rarely affected by cystic fibrosis.
Meconium periorchitis is the result of perforation of the
wall of the intestine in utero with subsequent extravasation
of meconium into the tunica vaginalis. It is sometimes present as a firm, nontender scrotal mass that is separate from
the testis and simulates a neoplasm.102 On gross examination, the tunica vaginalis and/or spermatic cord typically
displays numerous nodules composed of yellow-green material. However, masses measuring up to 3 cm in diameter have
been reported.102 The presence of numerous greenish-yellow
small nodules on the tunica vaginalis or spermatic cord in
young infants argues against a neoplasm. Microscopic examination shows myxoid tissue and spindle cells, macrophages,
squamous cells with and without nuclei, rare lanugo hairs,
and mesothelial hyperplasia.34 The lesion typically does not
have much inflammatory infiltrate.
Sperm Granulomas
Sperm granulomas occur at the superior pole of the epididymis or in the vas deferens.103,104 They are more common in
the vas deferens. They sometimes simulate neoplasms and
have resulted in orchiectomies.62,103–107 One patient with an
epididymal sperm granuloma had clinical features of an
intratesticular tumor.107 The lesion was associated with testicular swelling and pain 2 years after trauma, and ultrasound
studies revealed a solid, hypoechoic mass consistent with an
intratesticular tumor. The possibility of a sperm granuloma
should be considered when there is a firm, discrete, tender,
persistent nodule in the epididymis or vas deferens, especially if the patient has a history of a vasectomy.104
10/11/2013 11:43:10 AM
Chapter 13 n Pathology of the Paratesticular Region 815 More than 40% of sperm granulomas are related to a previous vasectomy,34 and 1% to 10% of men who have vasectomies develop sperm granulomas.104,108,109 Trauma, infection,
obstruction, and previous surgery are also associated with
this lesion. It may also be a complication of secondary oxalosis in patients with chronic renal failure.108 Most patients
are younger than 40 years of age.103
The average size of sperm granulomas is 7 mm, although
they may be as large as 4 cm, and they are sometimes multiple.104,106–110 They are firm, yellow-white lesions that contain sperm surrounded by neutrophils, histiocytes, and giant
cells. Cystic spaces may be present due to obstruction and
dilation of epididymal tubules, which may display squamous
metaplasia.34 Dystrophic calcification may occur. The lesion
eventually becomes replaced by fibrous tissue that may contain lipochrome pigment. Vasitis nodosa accompanies onethird of sperm granulomas present in the vas deferens.34
Vasitis Nodosa and Epididymitis Nodosa
Vasitis nodosa and epididymitis nodosa are usually postvasectomy changes. Vasitis nodosa is usually identified during
a vasovasostomy from 1 to 15 years after vasectomy.111 The
lesions occur in as many as half of men who have had vasectomies, and they may be bilateral. However, vasitis nodosa
and epididymitis nodosa may also follow trauma, herniorrhaphy, and prostatectomy.112 They have been described in
patients with primary infertility, chronic severe cystitis, and
bladder diverticula.112 Most cases are asymptomatic, possibly because the lesions are small (<1 cm). Some patients
have scrotal swelling, pain, and nodularity. Patients with
vasitis nodosa usually have a firm nodule in the scrotal part
of the vas. Both lesions display a proliferation of small ducts
and gland-like structures in the walls of the vas deferens
and epididymis in response to mechanical obstruction and
increased intraluminal pressure. The glands may be located
in a perineural location, resulting in confusion with adenocarcinoma.113–115 The gland proliferation seen in vasitis and
epididymitis nodosa does not display mitotic figures or
­epithelial atypia, and the presence of sperm in gland lumina
is evidence against a neoplasm. Extravasation of sperm leads
to sperm granulomas and subsequent inflammation and
fibrosis. Sperm granulomas coexist with vasitis and epididymitis nodosa in 70% of patients.34
Vascular Abnormalities and Ischemia
tender mass in the left spermatic cord of a 50-year-old man.
It was attached to a segment of a muscular artery, and the cut
surface showed aneurysmal dilation of the artery with blood
clot. There was a transition from the wall of the artery to the
aneurysm.118
Varicocele
Varicoceles represent abnormal venous dilation in the pampiniform vascular plexus. They occur in about 15% of men.119
They may be detected during investigation of infertility, or
they may present with scrotal pain and swelling. They occur
most commonly on the left side due to increased hydrostatic
pressure from the left spermatic vein entering the left renal
vein perpendicularly. The pampiniform plexus becomes
dilated and tortuous. More unusual causes of varicoceles
include compression of the renal vein, an aberrant renal vein,
or an obstructed renal vein.119 Varicoceles that occur on the
right side and those with recent onset in older men should
prompt evaluation of a possible abdominal mass compressing
veins downstream from the scrotum. Gross and microscopic
examination of the rete testis in patients with varicoceles often
reveals dilated rete testis veins that compress and obstruct
the rete tubules, although some patients have dilated efferent
ductule veins that result in dilated rete testis channels.120
Torsion
Testicular torsion has been diagnosed in one-third of patients
under the age of 40 who present with acute scrotal pain and
undergo emergency scrotal exploration.121 Torsion of the
spermatic cord results in hemorrhagic infarction of the testis. The next most common entity in the patients with acute
scrotal pain followed by emergency surgery is torsion of
the appendix testis. Torsion of the appendix testis has been
reported to be the most common cause of acute scrotum in
children.122 Torsion of the epididymis has been described in
a 11-year-old boy who presented with an acute scrotum and
was found to have an abnormal attachment of the epididymis to the testis.123 Torsion of the testicular or epididymal
appendages may simulate the clinical symptoms of testicular torsion. Gross and microscopic features of the structures
affected by torsion are those of hemorrhagic infarction. Dark
red, hemorrhagic tissue is present. Extravasated blood often
overshadows any residual parenchymal architecture, and
ischemic changes may obliterate normal histology.
Arterial Venous Malformations
Vasculitis
Arterial venous malformations are rare in the paratesticular
region. A case of an intrascrotal, extratesticular lesion was
detected after a bicycle accident resulted in a scrotal hematoma.116 A case has also been described in the spermatic cord.117
Some other arterial venous malformations have been reported
in the “scrotum” without specification of exact locations.
There has been one reported case of a spermatic artery
­aneurysm.118 It presented as a round, firm, nonpulsating
Polyarteritis nodosa is the most common vasculitis seen in
the paratesticular region.34 Unilateral or bilateral epididymal enlargement and tenderness may be either the presenting symptom of the disease or a component of s­ystemic
­disease.124–126 A review of autopsy tissue from patients with
known polyarteritis nodosa showed epididymal vasculitis in
two-thirds of cases.127 Isolated arteritis of the epididymis has
also been reported, and it may be either an incidental finding
Amin9780781782814_ch13.indd 815
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816 Urological Pathology
or associated with a mass.128 A case of limited Wegener granulomatosis involving the epididymis has been described in a
32-year-old man.129
Other types of vasculitis seen in the paratestis include
Henoch-Schoenlein purpura,130 thromboangiitis obliterans,
and granulomatous vasculitis. One 6-year-old boy with
Henoch-Schoenlein purpura developed a swollen, painful
right scrotum 24 hours after an appendectomy.130 The tunica
albuginea, epididymis, spermatic cord, and testis displayed
vascular necrosis, red blood cell extravasation, and vascular
infiltration by neutrophils.130 There was hemorrhagic infarction of the testis and spermatic cord. Microscopic examination displayed necrotic vessel walls with areas of acute
inflammation and extravasated red blood cells in the testis,
tunica albuginea, epididymis, and spermatic cord.
Thromboangiitis obliterans has been reported in the epididymis and spermatic cord.34 The patients reported have been
in the third or fourth decades of life, and they have presented
with firm, tender scrotal masses.131–133 Gross examination
of the lesions revealed enlarged, thickened vasa deferentia
or epididymal nodules. Microscopic examination displayed
arterial and venous thrombi and focal aggregates of mononuclear inflammatory cells and giant cells in the vessel walls.
Granulomatous vasculitis (Fig. 13-11) has been reported
in the epididymis or spermatic cord in five patients, either
with or without involvement of the adjacent testis.134–136 These
lesions have been unilateral or bilateral and synchronous or
metachronous. One 70-year-old patient had a painless paratesticular mass that was clinically suspicious for a neoplasm.
He had no signs or symptoms of vasculitis before resection
of the mass. Microscopic examination of the mass displayed
a nonnecrotizing granulomatous vasculitis containing giant
cells in arteries and veins of the spermatic cord.136
Two reported patients developed hemorrhagic infarction
of the testis as a result of intimal fibroplasia of the spermatic
artery.137 Both patients had orchiectomies because clinical ­features were suspicious for neoplasms. Microscopic
examination of both lesions showed moderate or marked
luminal obstruction of branches of the spermatic artery
under the tunica albuginea and in the testis. The arterial wall
intima contained a proliferation of loose connective tissue,
but there were no abnormalities of the elastic lamina. These
lesions resemble intimal fibroplasia of the renal artery seen
in patients with arterial hypertension.34
Miscellaneous Cysts, Celes and Pseudotumorous
Conditions
Cystic Transformation of the Rete Testis
(Synonym: Also Called Giant Cystic
Degeneration of the Rete Testis)
Nistal et al.138 studied 1,798 autopsy and 518 surgical specimens from the testis and epididymis, and identified cystic
transformation of the rete testis in 20 autopsy and 18 surgical pathology specimens.138 The cystic transformation was
thought to be due to several different etiologies. One cause
of this lesion is mechanical compression of the extratesticular excretory ducts, resulting from neoplasia or other masses
such as hematoceles. Cystic transformation may also follow
postvasectomy inflammation or it may be related to infection such as epididymitis. An ischemic etiology has also
been proposed in elderly men who have atherosclerosis in
the epididymal branch of the testicular artery with associated atrophy of the head of the epididymis. Hormonal abnormalities may cause cystic transformation of the rete testis in
patients with cirrhosis; these patients have increased peripheral conversion of androgen to estrogen and develop bilateral
epididymal atrophy and columnar transformation of the rete
testis epithelium. One case of giant cystic degeneration of
the rete testis has been reported recently in an elderly adult
man treated with LHRH for prostate adenocarcinoma.139 The
patient age, the postulated effect to antiandrogen therapy, and
the 10-cm size of the lesion are all unusual for this lesion.
Malformations, such as cryptorchidism, that have dissociation between the rete testis (derived from the sex cords) and
the epididymis (derived from the mesonephric duct) may also
result in cystic transformation of the rete testis (Box 13-2).
Box 13-2 l CELES/CYSTS OF THE PARATESTIS:
ETIOLOGY AND ASSOCIATED LESIONS
Cystic transformation
of the rete testis
Acquired cysts of the
rete testis
Cysts of the epididymis
Hydrocele (acquired)
F i g u r e 1 3 -11 n Granulomatous vasculitis involving the
­spermatic cord. Small blood vessels are surrounded by giant cells.
Amin9780781782814_ch13.indd 816
Hematocele
Mechanical compression, postvasectomy, ischemia, hormonal
factors, cryptorchidism
Hemodialysis
Polycystic kidney disease, von
Hippel-Lindau (rare), renal cell
carcinoma (rare), in utero DES
exposure
Idiopathic or may be secondary to
infection or neoplasm
Trauma, torsion, tumor, surgery
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Chapter 13 n Pathology of the Paratesticular Region 817 Acquired Cysts of the Rete Testis
Acquired cysts of the rete testis have been reported in patients
on hemodialysis, who may have oxalate crystals in the cyst
lumens140 (Box 13-2). Benign rete testis cysts are lined by a
single layer of flat or columnar epithelial cells.
atypia is not a feature of epididymal cysts. If spermatozoa
are present in the cysts, the lesions are called spermatoceles.
Small papillary structures containing connective tissue cores
lined by a single layer of bland epithelium may protrude into
the cysts.149
Mesothelial Cysts
Spermatocele
Mesothelial-lined cysts of the paratesticular area are rare and
may involve the tunica albuginea, tunica vaginalis, epididymis, or spermatic cord.18,141–144 They usually occur in men
over 40 years of age. They may either be asymptomatic or
patients may present with a painful mass simulating testicular tumors. These cysts may be single or multiple, but they
are usually unilateral and located on the anterolateral surface
of the testis.144 They measure from 0.3 to 0.4 cm in diameter
and contain serous or blood-tinged fluid. The cysts are lined
by single-layered, non-atypical, flattened, or cuboidal mesothelial cells. The epithelium is surrounded by hyalinized
connective tissue. Squamous metaplasia may be present.
The cysts are surrounded by fibrous tissue. They are benign
lesions that should be treated conservatively.
Spermatoceles result from cystic dilation of the efferent
ductules, the tubules of the rete testis, or the aberrant ducts.
Cysts may become large, with thin walls. Cloudy fluid present in spermatoceles is a result of sperm present in the cystic spaces. The fibromuscular walls are lined by cuboidal to
columnar, sometimes ciliated, epithelium. The epithelial lining of long-standing spermatocele may be quite attenuated
and may resemble a mesothelial or simple squamous layer.18
Sometimes they contain papillary proliferations lined by
benign epithelial cells.149 Calcification may occur.150 Clusters
of small blue cells have been reported in spermatocele and
hydrocele specimens. They may represent sloughed rete testis epithelium and they may mimic the appearance of small
cell carcinoma.151 Bland nuclei, lack of mitotic figures, and
lack of staining with neuroendocrine markers are features
indicative of benign epithelium.
Cysts of the Epididymis
Small benign cysts of the epididymis are common. They measure 1 to 2 cm in diameter. Pain and torsion may occur with
larger cysts.145 Polycystic kidney disease has been associated
with multiple epididymal cysts.146 Bilateral epididymal cysts
have been described in a patient with von Hippel–Lindau
disease and early-onset renal cell carcinoma.147 Epididymal
cysts have also been reported in 10% of men exposed to DES
in utero148 (Box 13-2).
Epididymal cysts usually occur in the head of the epididymis. They are thought to arise from efferent ductules.21
They may be unilocular or multilocular, and they are lined
by a single layer of flat to cuboidal epithelial cells that may
display variable numbers of cilia (Fig. 13-12). Cytologic
Dermoid and Epidermoid Cysts
Epidermoid cysts are rare in the paratestis.152 They present either incidentally during hernia repair procedures or
as painless enlarging masses located in the spermatic cord.
They are lined by keratinizing squamous epithelium and contain intracystic keratinous debris. Dermoid cysts have also
been reported in the spermatic cord.153,154 They contain skin
appendage structures in addition to squamous epithelium.
Most epidermoid and dermoid cysts are considered
benign neoplasms, in contrast to teratomas. Some epidermoid cysts may represent a metaplastic process derived from
mesothelium. The possibility of extension or metastasis
from a tumor in the testis should be excluded before making
this diagnosis.
Hydrocele (Acquired)
F i g u r e 1 3 -1 2 n Cyst of epididymis. A dilated, cystic efferent
duct is present adjacent to normal ducts.
Amin9780781782814_ch13.indd 817
A hydrocele is a fluid accumulation between the visceral
and parietal layers of the tunica vaginalis. Congenital hydroceles have been discussed above (congenital abnormalities). Acquired hydroceles may be idiopathic or secondary
to infections or neoplasms (Box 13-2). They represent the
most common cause of painless scrotal swelling. They form
over time, and neoplasm should be excluded in the case of a
rapid formation of a hydrocele. Hydroceles usually transilluminate, except in cases where the tunica vaginalis is thickened. Ultrasound shows an anechoic fluid collection. The
pathogenesis of acquired hydroceles reflects an imbalance
between fluid secretion and resorption in the tunica vaginalis.155 Defective lymphatic drainage has been suggested as a
cause of hydroceles.156
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818 Urological Pathology
Chronic hydroceles may become inflamed, with a
p­ roliferation of fibrous tissue. The testis may become adherent to the parietal tunica vaginalis. These features may mimic
neoplasms clinically.34,62,63 The resulting mass-like lesions
may be more than twice the normal size of the normal ­testis,
but they are diffuse and symmetrical.34 Patients in one series
of nine patients ranged from 22 to 88 years of age.63 Most
patients had hydroceles that were excised because of the
clinical similarity to neoplasms.63 Microscopic e­ xamination
showed features typical of a reactive process, including
­mesothelial hyperplasia with fibrosis and some chronic
inflammation.63 Organizing hemorrhage in a hydrocele may
also simulate a neoplasm until it is examined microscopically.
Hematocele
Hematoceles represent collections of blood in the tunica
vaginalis. They may be acute or chronic, and they may have
a mass effect. Causes include trauma, torsion, tumor, and
surgery (Box 13-2). Varicoceles may be present, and minor
trauma may cause rupture of one of the dilated blood vessels.69 Patients present with a mass and scrotal pain. Most
hematoceles resolve spontaneously with conservative therapy, but some may become fibrotic and calcified.157
Endometriosis
Endometriosis has been reported in an elderly man who presented with a mass in the tail of the epididymis on a followup examination after taking diethylstilbestrol for 3 years for
prostate carcinoma. On gross examination, a 5-cm mass was
present between the vas deferens and the tail of the epididymis. Microscopic examination showed tubular glands lined
by columnar to cuboidal epithelium without atypia. The
glands were surrounded by stroma typical of that normally
seen in the endometrium.
Prostatic-Type Glands
Prostatic-type glands have been found rarely in the epididymis.158 One example was found incidentally in a grossly
normal epididymis in a 30-year-old man.158 The glands displayed the two cell layers normally seen in prostate glands.
While these glands were different from the epididymal gland
epithelium, there was a focal transition from epididymal
ducts to the prostatic epithelium. The prostate glands stained
positively for prostatic acid phosphatase (PAP) and prostatespecific antigen (PSA), but some epididymal duct tissue was
also positive with these markers. The lesion probably represents prostatic metaplasia in the epididymis rather than true
ectopic prostate glands.158,159
Metanephric Dysplastic Hamartoma
There is one report of metanephric dysplastic hamartoma
presenting as an epididymal mass in an 18-month-old boy.
Blastema associated with papillae, glomeruloid structures, and dysplastic tubules were seen on m
­ icroscopic
Amin9780781782814_ch13.indd 818
­examination.5 This lesion must be distinguished from the
rare Wilms tumors that have been reported in the paratesticular region.
Rosai-Dorfman Disease
A few cases of Rosai-Dorfman disease (sinus histiocytosis
with massive lymphadenopathy) have been described in
the epididymis.160 Patients may be either children or adults,
and lymph nodes are also often involved.5 This process may
result in nodules, or it may diffusely involve the epididymis. Microscopic examination shows sheets of histiocytes
that contain oval nuclei and abundant pale cytoplasm with
poorly defined cell borders. The histiocytes may contain
phagocytosed lymphocytes, plasma cells, neutrophils, and
erythrocytes.
Calcification, Bone, and Cartilage
An autopsy study of testes and associated rete testes showed
a rare lesion called “nodular proliferation of calcifying connective tissue in the rete testis”161 in three men with histories
of myocardial infarction. Polypoid projections in the rete
spaces had connective tissue cores with calcification and
were covered by benign, flattened epithelial cells.
Calcification may cause firm nodules in the epididymis,
usually associated with sperm granuloma, filarial infection, or tuberculosis.162 Calcification of the epididymis may
also be seen in patients on hemodialysis.163 Two cases of
heterotopic bone trabeculae in the epididymis have been
reported.18,164 Cartilage has also been seen in the epididymis
of infants.165
Calcification of the seminal vesicles and vasa deferentia may indicate systemic disease.166 This lesion may be
associated with diabetes, uremia with secondary hyperparathyroidism, prostatitis, infections (tuberculosis, schistosomiasis, gonorrhoea), and congenital abnormalities.
Bilateral calcification of the vas deferens has been reported
in a hemodialysis patient167 and, rarely, the condition is
idiopathic.
Amyloidosis
One histochemical and ultrastructural study of six men with
secondary amyloidosis showed amyloid deposits in the walls
of the blood vessels of the epididymis and spermatic cord.168
Localized amyloidosis involving vasa deferentia has been
described in two patients with prostate carcinoma.169
Inflammatory Myofibroblastic Tumor
(Synonyms: Also Called Inflammatory
Pseudotumor, Pseudosarcomatous
Myofibroblastic Proliferation, and
Proliferative Funiculitis)
Inflammatory myofibroblastic tumor and related lesions in
the paratestis occur most often in the spermatic cord,62,170–176
but isolated cases have also been reported in the rete testis
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Chapter 13 n Pathology of the Paratesticular Region 819 F i g u r e 1 3 -1 3 n Inflammatory myofibroblastic tumor. A: Gross photograph showing circumscribed paratesticular tan tumor-like nodule; B: Note dense fibroblastic connective tissue and chronic inflammation adjacent to mesothelial lined space. Sclerosis is often present in
long-standing cases.
and epididymis.171,172 They may present as mass lesions, or
they may be incidental findings in inguinal hernia specimens.
Some of these lesions in the epididymis may be a reaction to
torsion and chronic ischemia.170,176
These lesions are usually gray or tan, firm nodules that
are <3 cm in size, although an occasional lesion has measured 7 cm.5 Some are well circumscribed (Fig. 13-13),
but many are poorly demarcated. Areas of hemorrhage
or cystic change may occur rarely. Inflammatory myofibroblastic tumors are composed of tapering spindle to
­stellate-shaped cells with vesicular nuclei and eosinophilic
cytoplasm. The stroma is fibrous or myxoid. Cellularity
varies in different parts of the lesions and may be greater
in the central portion of the lesion. Inflammatory and giant
cells may cause the lesion to resemble fasciitis seen elsewhere in the body.5 Hyalinized fibrous tissue characteristically surrounds blood vessels. The mitotic rate is usually
low, although torsion has been associated with greater
numbers of mitotic figures.176 Atypical mitotic figures
are not present. It is possible that these lesions may progress to the densely collagenous and hyalinized “fibrous
pseudotumors.”5 Immunohistochemical stains performed
on inflammatory myofibroblastic tumors show cells will
be of myofibroblastic phenotype; stains may be positive
for actins, vimentin, desmin, and sometimes keratin,34
although these stains are not usually necessary for diagnosis of this lesion.
The differential diagnosis of inflammatory pseudotumors
includes rhabdomyosarcoma, leiomyosarcoma, sclerosing
liposarcoma, malignant fibrous histiocytoma, and spindle
cell mesothelioma. The bland cytologic features, low mitotic
rate, lack of atypical mitoses, and overall resemblance to fasciitis are features that are helpful in recognizing the reactive
nature of this lesion and distinguishing it from malignant
neoplasms.
Amin9780781782814_ch13.indd 819
Fibrous Pseudotumor (Synonyms: Called
Fibromatous Periorchitis, Nodular Periorchitis
Additional Synonyms: Chronic Periorchitis,
Proliferative Funiculitis, Fibrous Proliferation
of Tunics, Fibroma, Nonspecific Testicular
Fibrosis, Nodular Fibrous Periorchitis,
Nodular Fibrous Pseudotumor, Inflammatory
Pseudotumor, Reactive Periorchitis,
Pseudofibromatous Periorchitis)
Paratesticular fibrous pseudotumors present as mass
lesions. They are most often seen in the third decade of
life,177,178 but one case has been reported in a 5-year-old
boy.179 One patient had retroperitoneal fibrosis, one had
Gorlin syndrome,180 and one lesion was associated with
testicular infarction.181 After adenomatoid tumors, these
lesions represent the most common cause of masses in
the paratestis. Patients have single or multiple nodules
or plaques in the tunica vaginalis,182,183 epididymis,184,185
or spermatic cord, and the nodules range from 0.5 to
F i g u r e 1 3 -1 4 n Fibroma of the tunica vaginalis. Gross
p­ hotograph showing extensive involvement of tunica vaginalis by
white nodular fibrous tissue.
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820 Urological Pathology
8 cm177 (Fig. 13-14). In a diffuse form, dense fibrous tissue
involves the tunica vaginalis.
Microscopically, this lesion is characterized by dense, hyalinized, fibrous tissue often containing lymphocytes and plasma
cells with occasional germinal centers.186 Calcification and
ossification may occur.187 Three histologic types of fibrous
pseudotumor have been recently described,188 although this subclassification is mainly of academic i­ nterest. Plaque-like lesions
have dense fibrous stroma without significant inflammation,
inflammatory sclerotic pseudotumors contain dense fibrous
­tissue with significant inflammation and myofibroblastic lesions
have reactive appearing cells with numerous capillaries and
sparse chronic inflammation.188 Paratesticular fibrous pseudotumor does not display significant nuclear atypia, mitotic activity,
or necrosis. The differential diagnosis of paratesticular fibrous
pseudotumor includes solitary fibrous tumor, leiomyoma, fibromatosis, spindle cell mesothelioma, and neurofibroma.188
Immunohistochemical stains performed on paratesticular
fibrous pseudotumors display positive staining for smooth
muscle actin in more than 80% of cases.188 Surprisingly,
stains for cytokeratin, calretinin, and CD34 are positive in
about half of the cases.188 All cases in a recent study were
negative for B-catenin and ALK-1, and these lesions have a
very low proliferation index as measured by Ki-67 staining.188
Potential cells of origin include myofibroblasts and
submesothelial stromal cells, but paratesticular fibrous pseudotumors may be a nonspecific pattern resulting from a variety of pathogenetic processes.188 Past histories of trauma,
surgery, infection, and inflamed hydroceles in some patients
suggest a reactive etiology,63,189 although some patients have
no such prior events. Some fibrous pseudotumors are thought
to represent an advanced stage of inflammatory pseudotumors.149,177,190 Paratesticular fibrous pseudotumors are benign
lesions, and local excision is curative.
“Tumor” of the Adrenogenital Syndrome
and Related Lesions
This lesion develops in the paratesticular region of men with
the adrenogenital syndrome who are not adequately treated,
especially men with the salt-losing form of the syndrome.
Nodules of steroid-type cells may occur in the epididymis, the
spermatic cord, or the tunica albuginea.38,191–193 The paratesticular lesions may either extend from testicular nodules or be
separate dark brown nodules measuring up to 1.5 cm in diameter.38 Sometimes, fibrous septa are present in the nodules.
The microscopic appearance of these lesions is quite characteristic. Paratesticular nodules of steroid type cells are present.
Bands of fibrous tissue and focal nuclear atypia are also seen.
Five cases of rete testis–associated nodular steroid cell
nests associated with the rete testis have recently been
reported.194 They are discrete conspicuous, unencapsulated
nodules with vascular sinusoids between nests or cords of
cells. They display strong melan A immunostaining, absentto-weak inhibin staining and absent-to-moderate calretinin
Amin9780781782814_ch13.indd 820
expression, in contrast to interstitial Leydig cells and
­testicular adnexal Leydig cells (TTAGS). The cells in rete
­testis–associated nodular steroid nests have been postulated
to represent the precursor of testicular tumors of the adrenogenital syndrome.194
Patients with Nelson syndrome have ACTH-secreting
pituitary adenomas following bilateral adrenalectomy for
Cushing syndrome. These patients may also develop paratesticular steroid cell nodules.39,195,196 All reported cases have
been bilateral, with nodules ranging up to 5.5 cm in diameter.195,196 They may produce cortisol and result in recurrence
of Cushing syndrome. Gross and microscopic features are
similar to those seen in patients with the adrenogenital syndrome. Bilateral small steroid cell nodules have also been
described in children with Cushing syndrome and nodular
hyperplasia of the adrenal cortex.38,197 They also have the
same morphologic characteristics as the nodules associated
with the adrenogenital syndrome.
Some masses of paratesticular steroid cells may also
develop by stimulation of ectopic adrenocortical tissue found
in about 10% of infants and some older patients.5,34,35,198,199
Hyperplasias
Hyperplasia of the Rete Testis (Synonym: Also
Called Adenomatous Hyperplasia)
Hyperplasia of the rete testis includes both epithelial hyperplasia and smooth muscle hyperplasia. Epithelial hyperplasia
may be real or apparent, so-called rete testis prominence.200
The cause of rete testis hyperplasia is not clear, but it may
reflect hormonal factors including estrogen effect.201,202 Mice
exposed in utero to DES have developed rete hyperplasia.203
Cryptorchidism, thought to be related to abnormalities of the
hypothalamic–pituitary–testicular hormonal axis, is associated with both testicular atrophy and rete testis hyperplasia.204 One reported patient had been treated with DES for 15
months and androgen blockade for 19 months before diagnosis of rete testis hyperplasia.201 Increased numbers and stratification of rete epithelial cells has also been described after
estrogen therapy in male-to-female transsexual patients.202
Columnar change of the rete epithelium has been associated
with chronic liver failure,202 further supporting a hormonal
basis for hyperplasia of the rete testis. Rete testis hyperplasia may also be associated with testicular atrophy and hypospermatogenesis.13,18,201,205,206 There is no clear dividing line
between prominent rete testis associated with testicular atrophy and true rete hyperplasia. Rete hyperplasia may also be
associated with epididymal cribriform change.13 It has also
been described in a child with bilateral renal dysplasia207 and
in patients with carcinoma of the prostate208 and breast.205
Some authors have proposed separating hyperplasia of
the rete testis into two types: congenital and acquired.209
Lesions associated with cryptorchid testes, as well as some
that are associated with testicular germ cell tumors, are
included in the congenital group. Cases related to chemical
10/11/2013 11:43:14 AM
Chapter 13 n Pathology of the Paratesticular Region 821 F i g u r e 1 3 -1 5 n Adenomatous hyperplasia of rete testis.
Complex, interconnecting proliferation of tubular channels with
and without cystic dilation, low power (A, B). The lining cells are
cuboidal to low columnar with innocuous cytology (C). (Reprinted
from Amin MB. Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial
lesions and secondary tumors. Mod Pathol 2005;18:S131–S145,
with permission.)
agents, some hormonal changes such as androgen blockage,
and most lesions related to testicular germ cell tumors are
considered acquired hyperplasias.
Nine patients in one study of rete testis hyperplasia201
ranged in age from 30 to 74 years of age (mean 59 years).
Three patients presented with a clinically identifiable solid
or cystic testicular hilar mass; however, the lesion is more
likely to be an incidental finding. Rete testis hyperplasia may
be multinodular and/or bilateral.
Two histologic types of rete testis hyperplasia have been
described. Adenomatous hyperplasia (Fig. 13-15) displays
a complex focal or diffuse interconnecting labyrinth of
tubulopapillary channels that may be cystically dilated.200
Gland lumina may be empty or they may contain either
sperm or eosinophilic secretions. A second type of rete testis hyperplasia represents an incidental finding in patients
with testicular germ cell tumors. This lesion is characterized by a focal or diffuse epithelial proliferation within
dilated rete testis spaces (Fig. 13-16). Hyaline globules
within the hyperplastic rete epithelium may simulate the
appearance of yolk sac tumor. Cells of rete hyperplasia are
Amin9780781782814_ch13.indd 821
cuboidal, with pale, eosinophilic cytoplasm and round to
oval, uniform nuclei. There is no cytologic atypia, necrosis, or mitotic activity. Epithelial cells stain positively for
cytokeratin and epithelial membrane antigen, and the mesenchyme between the hyperplastic tubules displays variable
staining for vimentin, muscle-specific actin, desmin, and
S-100 protein.201 Ultrastructural examination of the epithelial cells shows intracellular junctions and complex interdigitation of cell membranes.201 Important indicators of the
benign, reactive nature of this lesion are overall conformation to the normal branching tubular architecture of the rete
testis and its continuity with nonhyperplastic rete testicular
tubules.
Rete testis hyperplasia may resemble a primary or metastatic carcinoma.5,18,21,201,205,208 PSA and PAP stains may
be useful in distinguishing rete hyperplasia from prostatic carcinoma.206 Testicular germ cell tumors may be
associated with papillary, squamous, or vacuolated rete
testis epithelium.210 Furthermore, there may be invasive
or intraepithelial pagetoid spread of the germ cell tumor
in the rete testis.210–213 Immunohistochemical stains for
10/11/2013 11:43:17 AM
822 Urological Pathology
F i g u r e 1 3 -1 6 n Rete testis hyperplasia associated with germ cell tumor. Hyperplastic rete e­ pithelium fills expanded channels (low
power) (A). Seminoma associated with rete testis hyperplasia (B). Hyperplastic rete epithelium shows intracytoplasmic and extracellular
hyaline globules that result in an appearance simulating yolk sac tumor. If misinterpreted as such, this would lead a pure seminoma to be
diagnosed as a mixed germ cell tumor with seminoma and yolk sac tumor components. (Reprinted from Amin MB. Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and pseudotumor, mesothelial lesions and secondary tumors. Mod Pathol
2005;18:S131–S145, with permission.)
germ cell tumors can resolve any diagnostic c­ onfusion.214
Rete testis hyperplasia may contain eosinophilic hyaline
globules that are P
­ AS-positive and may stain for alpha1-anti-trypsin, but they are alpha-fetoprotein negative.
They may contain proteins absorbed from the rete lumen
by lining epithelial cells.210 Rete hyperplasia with hyaline
globules needs to be distinguished from the many and
various morphologic patterns of yolk sac tumor.210,215 One
case of rete testis hyperplasia with hyaline globules also
had eosinophilic basement membrane material between
the hyperplastic rete epithelial cells, simulating the parietal type of yolk sac tumor.210,215 Papillary adenoma of the
rete testis, a small lesion that is usually identified incidentally in the testicular hilum at the time of microscopic
examination, also needs to be distinguished from rete
­testis hyperplasia.
atypia has been attributed to fusion of epithelial cells
into multinucleated giant cells that then form large pyknotic nuclei.34 These atypical nuclei are more frequently
encountered in older patients and are not associated with
any systemic disease, but the association with age supports a hormonal or degenerative process.34 This is a focal
or spotty process, and the atypical nuclei may contain
cytoplasmic pseudoinclusions, but there are no mitotic
figures.
Reactive Mesothelial Hyperplasia
Reactive mesothelial hyperplasia is an uncommon lesion
that may be associated with hydrocele, hematocele, hernia
sacs, and paratesticular fibrous pseudotumors.18,149,217 It is
Cribriform Hyperplasia and Atypical Nuclei in
the Epididymis
The normal epididymis, which usually has a simple columnar epithelium, may display a cribriform epithelial pattern
(Fig. 13-17).15,216 The cribriform change is usually focal but
can sometimes be more extensive raising the possibility of
hyperplasia, although the latter has not been well defined in
the epididymis. The incidence of this histologic finding has
ranged from 8% to 50% in the literature.13–15 Intratubular
confinement of the cribriform epithelium and lack of mitotic
activity or cytologic atypia are features that are helpful in
distinguishing this architectural variant from epididymal
carcinoma.
Enlarged and atypical nuclei similar to those seen in
the seminal vesicles may also occur in the efferent ductules, ductus epididymis,9 and vas deferens. This cytologic
Amin9780781782814_ch13.indd 822
F i g u r e 1 3 -1 7 n Cribriform architecture in the epididymis.
The cells are cuboidal or columnar. There are no mitotic figures.
10/11/2013 11:43:19 AM
Chapter 13 n Pathology of the Paratesticular Region 823 F i g u r e 1 3 -1 8 n Reactive mesothelial hyperplasia with
­mesothelial entrapment occurring in a background of organizing
hematocele. Low-power observation of linear disposition of tubules
rather than a haphazard infiltrative growth is an important feature to
recognize (A). Higher power shows small reactive tubulopapillary
mesothelial clusters with retraction artifact that may mimic vascular invasion (B). Immunohistochemical stain for WT1 confirms
the mesothelial nature of the proliferation (C). (Reprinted from
Amin MB. Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial
lesions and secondary tumors. Mod Pathol 2005;18:S131–S145,
with permission.)
usually an incidental histologic finding in those lesions, and
it appears to be a response to serosal injury.200 Mesothelial
hyperplasia usually displays submesothelial aggregates of
mesothelial cells that are well circumscribed and surrounded
by fibrous tissue.218 Small papillary structures and solid nodules of mesothelial cells may also protrude into the lumen of
the involved structure. Most cases show no cytologic atypia,
but nuclear atypia and rare mitoses217 are present in some
cases. The combination of the mesothelial proliferation and
submesothelial fibrosis may result in clusters of mesothelial cells or small glands being trapped in fibrous tissue in a
pseudoinvasive pattern. The overall proliferation, however,
has a linear distribution without destructive invasion of the
underlying tissue (Fig. 13-18).
Reactive mesothelial hyperplasia must be distinguished
from well-differentiated papillary mesothelioma, malignant
mesothelioma, paratesticular serous tumors, and metastatic
adenocarcinoma. Reactive mesothelial hyperplasia lacks the
significant cytologic atypia and invasive or complex destructive tubulopapillary pattern seen in malignant tumors,144
and it often contains inflammatory cells. It does not form
a mass lesion. A desmin immunohistochemical stain may
be useful in differential diagnosis because it stains reactive
Amin9780781782814_ch13.indd 823
mesothelial cells but not malignant mesothelial proliferations.219 The presence of mesothelial immunohistochemical
markers220 and the lack of an invasive pattern are useful in
excluding adenocarcinoma.
Smooth Muscle Hyperplasia
Smooth muscle hyperplasia of the testicular adnexa represents an idiopathic overgrowth of muscle normally present in the paratesticular region. It proliferates around or
between normal structures.221 The largest series of these
unusual lesions reported 16 cases that involved the epididymis, the spermatic cord, the tunica vaginalis, and the tunica
albuginea.221
Smooth muscle hyperplasia in the paratestis has been
seen in adults between 46 and 81 years of age.221 All patients
presented with palpable intrascrotal mass lesions ranging
from a few millimeters to several centimeters in diameter.
The average size was 2.5 cm, but some of these masses measured up to 7 cm in diameter. Some were nodular or fusiform
masses, whereas others were more poorly defined thickenings of paratesticular structures. Gross examination showed
firm gray to white cut surfaces.34 Microscopic examination
10/11/2013 11:43:22 AM
824 Urological Pathology
revealed a diffuse or nodular increase in smooth muscle that
displayed a perivascular, periductal or interstitial location.221
No inflammatory infiltrate or mitotic figures were seen in the
smooth muscle hyperplasia. The well-circumscribed architecture seen in leiomyomas was not present. Proliferations of
smooth muscle surrounded the vas deferens and epididymal
ducts. This lesion was associated with vasitis nodosa, interstitial fibrosis, calcium deposition, and duct ectasia in some
cases. One case of simultaneous leiomyoma and contralateral smooth muscle hyperplasia of the epididymis has been
reported.222 A complex cystic mass of the rete testis associated with smooth muscle hyperplasia and myxoid stroma
containing Leydig cells has also been described in a 26-yearold man.223 Smooth muscle hyperplasia of paratesticular
structures is a benign lesion that does not recur after excision.
Multicystic Mass of Probable Wolffian Origin
A multicystic mass of presumed wolffian origin in the paratestis displayed multiple cysts lined by cuboidal to columnar
epithelium and surrounded by strands of smooth muscle and
was considered to represent cystic hyperplasia of wolffian
duct remnants.224
NEOPLASMS OF THE PARATESTICULAR REGION
Epithelial Tumors
Rete Testis and Epididymis—General
Considerations
Primary tumors of the rete testis are rare. Pagetoid or direct
stromal extension of tumors from the testis and metastatic
tumor from other sites are seen more commonly than primary rete testis tumors. Primary tumors are seen in the hilar
aspect of the testis and are continuous with the branching
channels of the normal rete. The hilar location is apparent in
small tumors. The site of origin of larger neoplasms may not
be apparent on gross examination.
Only 5% of intrascrotal neoplasms arise in the epididymis.225 One large series of epididymal tumors found that
75% were benign and 25% were malignant.226 The most
common tumor seen in the epididymis is adenomatoid
tumor. Papillary cystadenomas, leiomyomas, and lipomas also occur at this site.149 Most primary malignant
tumors of the epididymis are sarcomas, but carcinomas,
primary germ cell tumors and metastatic tumors may be
encountered.227,228
Benign Tumors of the Rete Testis
Benign epithelial tumors of the rete testis are rare. They
have been called adenomas,229 benign papillary tumors,230
cystadenomas,231 papillary cystadenomas,232 and adenofibromas.233 These neoplasms have occurred in patients between
12 and 51 years of age; the average age has been 26 years.
Patients with these tumors have unilateral scrotal masses.
Amin9780781782814_ch13.indd 824
These tumors are well-circumscribed, usually solid masses
of the rete testis. Cystic and mixed cystic and solid masses
also occur.231 Tumors range from 1.5 to 3.6 cm in diameter.21
Smaller tumors may be incidentally found during microscopic examination of the rete testis. Microscopic examination shows cysts and intracystic papillary structures lined by
cuboidal cells without atypia or mitotic figures. A transition
with normal rete channels is helpful in making the diagnosis. A rare adenofibroma has been reported.233 It displayed
a fibrous tissue component in addition to short tubules and
longer slit-like spaces lined by cells similar to those of the
normal rete testis.
Five cases of sertoliform rete cystadenoma21,231,234 have
all contained solid tubules resembling those seen in testicular Sertoli cell tumors (Fig. 13-19). The similar appearance of solid tubules in sertoliform rete cystadenomas and
Sertoli cell tumors of the testis reflects the common sex cord
embryogenesis of the rete testis and testicular sex cord elements.235 One sertoliform rete cystadenoma showed small
areas of tumor at the junction of the rete with the seminiferous tubules.21 Some authors21 have suggested that the origin
of sertoliform cystadenomas is from the “transition zone”
between rete and seminiferous tubules. Since both anatomic
structures develop from gonadal sex cord tissue, cells in
the rete testis near the seminiferous tubules may have the
capacity to differentiate toward Sertoli cells. The presence
of inhibin positivity in one tumor21 further supports this
hypothesis. It is important to distinguish primary rete testis
tumors from secondary rete involvement by adjacent Sertoli
cell tumors of the testis.236 Location of the tumor in the rete
testis only, not accompanied by a coexisting testicular Sertoli
cell tumor, a noninvasive growth pattern, and lack of nodular
aggregates of cells are features supportive of a primary rete
testis tumor.21 Inhibin staining is not helpful in distinguishing between rete testis cystadenomas and testicular Sertoli
cell tumors, since it stains both tumors.21
Benign Tumors of the Epididymis
Papillary cystadenomas237–239 and cystadenofibromas240 are
benign tumors that occur in men from 16 to 65 years of age
(mean 36 years). They usually present as palpable, nonpainful masses in the head of the epididymis.238,239 About onethird of epididymal tumors are papillary cystadenomas, and
about two-third of these occur in patients with von HippelLindau syndrome.238,239,241–243 More than half of patients with
this syndrome develop unilateral or bilateral epididymal
cystadenomas,239 and the cystadenoma may be the initial sign
of the syndrome.238 Most bilateral tumors are associated with
von Hippel-Lindau syndrome238,239,241–243 but some bilateral
tumors are nonsyndromic.238,244 Most patients developing
epididymal cystadenomas in the absence of von HippelLindau syndrome have unilateral tumors.238,241,245 A molecular pathology analysis of epididymal cystadenomas collected
from von Hippel-Lindau patients at autopsy demonstrated
that these lesions are true neoplasms that arise following a
10/11/2013 11:43:22 AM
Chapter 13 n Pathology of the Paratesticular Region 825 F i g u r e 1 3 -1 9 n Sertoliform cystadenoma of the rete testis.
The neoplasm expands the native rete. Low power (A). Elongated
trabeculae and solid tubules of tumor resembling a Sertoli cell tumor
(B). Inhibin positivity (C). Note the nonneoplastic rete epithelium
is also positive for inhibin. (Reprinted from Amin MB. Selected
other problematic testicular and paratesticular lesions: rete testis
neoplasms and pseudotumors, mesothelial lesions and secondary
tumors. Mod Pathol 2005;18:S131–S145, with permission.)
sequence of inactivation of the wild-type copy of the von
Hippel-Lindau gene, and activation of hypoxia-inducible factor.246 The epididymal cystadenomas in von Hippel-Lindau
patients are thought by some authors to evolve from a subset
of microscopic epithelial tumorlets in the efferent ductular
system.246 Sporadic tumors do show a mutation in the von
Hippel-Lindau gene,247 and some authors have suggested
that unilateral, sporadic epididymal cystadenomas represent
a forme fruste of this disease.21 Epididymal cystadenomas
may cause infertility and obstructive azoospermia.242,248,249
On gross examination, epididymal cystadenomas are
well-circumscribed masses in the head of the epididymis.
Most are relatively small, but sizes as large as 5 cm have
been reported.238 These tumors may be solid, cystic, or partially cystic, and they are usually gray-tan in color.238,245
Small, fluid filled cysts may be seen on cut sections.238
Microscopic examination reveals tubules, cysts, and
papillary structures lined by one or two layers of bland,
cuboidal to columnar epithelial cells that may be ciliated
(Fig. 13-20).237,238,242 Cystic fluid or an eosinophilic colloid
material may be present. The cells lining this lesion have vacuolated or clear cytoplasm that contains glycogen.242 Efferent
ductules may be ecstatic.242 Solid cores of clear cells may be
present in the cyst walls.21 While the epithelium of this tumor
Amin9780781782814_ch13.indd 825
contains glycogen238,245 and fat,245 mucin is not present.238
Cytokeratin, epithelial membrane antigen, and carcinoembryonic antigen all are positive in the tumor cells.244
The papillary cystadenomas of the epididymis generally
have a characteristic appearance, and the diagnosis is usually
straightforward. However, it is important not to confuse papillary cystadenoma composed of cells with clear cytoplasm
with clear cell carcinoma of the epididymis. Cystadenomas
lack the invasive pattern, nuclear atypia, and mitoses seen
in clear cell carcinoma. Metastatic renal cell carcinoma
may metastasize to the paratesticular region, but the prominent thin-walled blood vessels characteristically situated
between nests of clear cell carcinoma of the kidney are not
seen in epididymal cystadenomas. Immunohistochemical
stains performed on epididymal cystadenomas are negative for RCC antigen and CD10, in contrast to renal cell
carcinomas.250
Benign Ovarian-Type Epithelial Tumors
Ovarian-type epithelial tumors occur infrequently in the paratesticular region, and they are identical to their more frequent
counterparts in the ovary. Benign ovarian-type epithelial
tumors include serous cystadenoma, mucinous cystadenoma,
10/11/2013 11:43:25 AM
826 Urological Pathology
F i g u r e 1 3 - 2 0 n Papillary cystadenoma of epididymis. A: Note tightly packed papillae lined by small cuboidal cells with clear
cytoplasm; (B) cuboidal epithelial cells with small uniform nuclei and clear cytoplasm are seen. (Images courtesy of Dr Jonathan Epstein,
Baltimore, MD.)
and Brenner tumor. Ovarian-type epithelial tumors are ­usually
seen in adults, and they typically present as mass lesions.5
Two serous cystadenomas of ovarian type have been
reported in the epididymis.251,252 These are cystic lesions
that may be surrounded by ovarian-type stroma. These cysts
are often translucent and thin-walled. They typically have
smooth linings, but a few blunt, club-shaped papillary processes may occur. Microscopically, the cysts are lined by
a single layer of ciliated cells that suggest derivation from
müllerian duct remnants. There is no epithelial stratification,
tufting, or atypia in these lesions. Immunohistochemical
stains are not necessary for the diagnosis of serous cystadenomas, and the ciliated lining distinguishes serous lesions
from mesothelial cysts. The presence of ovarian stroma associated with benign serous tumors is not seen in epididymal
cysts, which also may contain ciliated epithelium.
Paratesticular mucinous cystadenomas have been
reported adjacent to the testis and in the spermatic cord.253
Mucinous cystadenomas are cystic lesions that are usually
translucent on gross examination. They may be multilocular, but they do not contain solid or necrotic areas. They are
usually lined by a single layer of endocervical-type mucinous epithelium that does not display tufting, stratification,
atypia, or mitoses, but one paratesticular mucinous cystadenoma has been lined by intestinal-type mucinous epithelium.254 One reported case had smooth muscle in its wall and
had ruptured, with mucin extravasation.253 The diagnosis is
straightforward if one remembers that ovarian type lesion
can arise in the paratesticular region. Immunohistochemical
stains are not of much use. The etiology of benign mucinous tumors of the paratesticular region has been a topic of
debate. Origin of a mucinous cystadenoma from the ovarian
component of a dysgenetic gonad has been considered,255 but
these lesions may also arise from metaplastic mesothelium,
from müllerian remnants,254 or from the mucinous components of teratomas.253
Amin9780781782814_ch13.indd 826
Brenner tumors of the paratesticular region are firm,
white or tan masses that are predominantly solid, but they
may contain scattered small cystic spaces. Microscopic
examination reveals fibrous stroma surrounding nests of
urothelial-type epithelium that often contain longitudinal
nuclear grooves (Fig. 13-21). Cystic spaces lined by columnar or cuboidal mucinous epithelial cells may be present
within the epithelial nests. The diagnosis is straightforward,
and no ancillary studies are necessary. Brenner tumors most
likely arise from metaplastic mesothelium, where Walthard
cell nests also occur.51,256 It is not unusual to find Walthard
cell nests in the mesothelium at the junction of the testis and
epididymis. A Brenner tumor associated with an adenomatoid tumor has been reported, further supporting derivation
of Brenner tumors from mesothelium.257
Malignant Epithelial Neoplasms
Carcinoma of the Rete Testis
Primary carcinomas of the rete testis are rare tumors,
although they are more common than benign rete testis
tumors.258,259 They have been reported only in Caucasian
men. While patients have ranged from 8 to 91 years of
age, 70% of reported cases have been in men over the age
of 60 years.21,259,260 Both rete testes are involved with equal
frequency. Most patients present with scrotal pain or swelling.200 Some have clinical features suggesting inflammatory disorders such as epididymitis rather than a mass
lesion,260,261 and a clinical presentation that does not suggest
neoplasm may delay the correct diagnosis. One quarter of
reported cases have been associated with a hydrocele259,262
that may mask the underlying tumor and delay detection of
the neoplasm.263,264 Since the tumor is most often located
on the posterior aspect of the testis, it may be difficult to
palpate. Patients with advanced neoplasm may have tumor
nodules occur on the scrotal skin, penis, or the perineum,260
10/11/2013 11:43:28 AM
Chapter 13 n Pathology of the Paratesticular Region 827 F i g u r e 1 3 - 2 1 n Brenner tumor of testis. Gross appearance of
multiloculated cystic tumor that replaces the testis (A). Low power
of cystic component of tumor (B). Solid area shows more characteristic histology of Brenner tumor (C). (Reprinted from Amin MB.
Selected other problematic testicular and paratesticular lesions: rete
testis neoplasms and pseudotumors, mesothelial lesions and secondary tumors. Mod Pathol 2005;18:S131–S145, with permission.)
and draining sinuses may occur265 in some patients. The
p­ rognosis for patients with adenocarcinoma of the rete testis is very poor. The average survival is 8 months, although
survival of over 4 years has been reported.200 The etiology of
these neoplasms is not clear. Carcinomas do not arise from
cystadenomas, although there is one report of a patient with
a history of rete testis hyperplasia who subsequently developed a rete adenocarcinoma.266 Some younger patients have
had a history of testicular maldescent,267 and one case has
been associated with asbestos exposure.262
It is likely that some tumors formerly diagnosed as rete
testis carcinomas actually represent other entities such as
serous neoplasms. Nochomovitz and Orenstein259 listed five
criteria for the diagnosis of rete testis tumors: (1) absence of
tumor with similar histologic features outside the scrotum,
(2) tumor centered in the testicular hilus, (3) morphologic
features not consistent with another testicular or paratesticular tumor type, (4) a transition exists between the tumor
and the normal rete testis, and (5) a predominantly solid
architecture. More recently, Amin200 added the additional
requirement for immunohistochemical exclusion of other
paratesticular malignancies, such as malignant mesothelioma and papillary serous carcinoma. The requirement for
a predominantly solid architecture is not absolute. We now
recognize that rete testis carcinomas can have cystic areas,
Amin9780781782814_ch13.indd 827
and that not all cystic rete tumors are of serous derivation,
although it is likely that some cases reported in the earlier
literature, especially those with longer survivals, actually
represent serous tumors.21 It may be difficult to see the transition between the rete carcinoma and the uninvolved rete
testis. The first three criteria of Nochomovitz and Orenstein
and the additional criterion proposed by Amin should be met
for a diagnosis of rete testis adenocarcinoma.21,200
Careful attention should be given to the location of the
tumor in the hilar region of the testis on gross examination
of the specimen; this location suggests a rete testis origin for
the neoplasm. Rete testis carcinomas are most often large
solid tan masses that range from 6 to up to 12 cm in size.21,263
Rare tumors may have cystic areas5,259–261,268 that contain
fluid. Areas of hemorrhage and necrosis may be present.269
Satellite tumor nodules may be seen in the tunica albuginea.
About one-third of tumors extend into other paratesticular
structures, including the spermatic cord,259,260 but spermatic
cord involvement may be apparent only on microscopic
examination.260,269,270
Microscopic examination of these neoplasms shows
solid, glandular, and papillary nodules of tumor (Fig. 13-22).
Papillary structures may project into cysts.235,260–263,267–270
Tubular and glandular structures often have elongated, slitlike shapes, or even a sertoliform appearance.235 A retiform
10/11/2013 11:43:33 AM
828 Urological Pathology
F i g u r e 1 3 - 2 2 n Adenocarcinoma of rete testis. Note infiltrating adenocarcinoma with a tubulopapillary growth pattern
­associated with fibrous stroma.
pattern displays elongated and compressed branching
tubules.200 Many neoplasms display confluent growth of
tumor cells.235,259,263,269,270 A Kaposiform pattern has been
described and is mainly solid with scattered very small, slitlike channels.200 Tumor cells have enlarged, hyperchromatic
nuclei, but marked pleomorphism is not usually seen. The
mitotic rate is variable, and areas of necrosis may be present. Tumors with a cellular spindle-cell component have
been reported.269,270 Transition between benign rete testis
epithelium, atypical epithelium, and the carcinoma is helpful in establishing the diagnosis, but it may be difficult to
identify.259,260,271
Special stains and immunohistochemical stains are not
specific for carcinomas of the rete testis, but they are very
useful in excluding other lesions such as mesothelioma or
papillary serous carcinoma (Box 13-3). Carcinomas of the
rete testis do not usually contain mucin. They are diffusely
reactive for cytokeratin and EMA,269,270 even when a spindle cell component is present in the tumor. CEA has been
detected in these tumors by some investigators, but not by
others.208,239,240 These tumors do not stain for hCG, AFP,
S-100 protein, Leu-M1, placental alkaline phosphatase, or
PSA.235,269 Stains for malignant mesothelioma and serous
Box 13-3 l LIKELY IMMUNOHISTOCHEMICAL
REACTIONS IN TUBULOGLANDULAR
NEOPLASMS*
Malignant
mesothelioma
Papillary serous
carcinoma
Rete/epididymal
carcinoma
Metastatic
carcinoma
WT1+, calretinin+, thrombomodulin±,
Leu M1−, CEA−, CK7+, CK20−
WT1+, CA 125+, Leu M1±, CEA±,
­calretinin±, thrombomodulin±, CD10±
CD10+, calretinin±, Leu M1±, CEA±,
WT1−, Thrombomodulin±
Lung (CK7+, CK20−, TTF1+, Leu M1+),
colorectal (CK7−, CK20+, CDX2+, CEA+)
Prostate (CK7−, CK20−, PSA+, PLAP+)
*Redrawn from Amin MB. Selected other problematic testicular and
paratesticular lesions: rete testis neoplasms and pseudotumors,
mesothelial lesions and secondary tumors. Mod Pathol 2005;18:
S131–S145, with permission.
Amin9780781782814_ch13.indd 828
carcinoma should be performed to exclude those ­possibilities
before a diagnosis of rete testis adenocarcinoma is made.
Malignant mesotheliomas are positive for calretinin, WT-1,
CK5/6, and negative for CEA, Leu-M1, Ber EP4, and B72.3.
Serous carcinoma stains positively for CA-125 and WT-1.
Electron microscopic examination of adenocarcinomas
of the rete testis shows cells with oval to irregular nuclei
and sometimes deep nuclear indentations. One or two nucleoli are present, and microvilli are variable in number.260,269
Cytoplasm contains variable amounts of smooth and rough
endoplasmic reticulum, rod-shaped mitochondria, and occasional clusters of tonofilaments, but the Golgi apparatus is
poorly developed and microvilli lack core rootlets.260,269–271
While lipid and glycogen may be present, mucin vacuoles
are not identified.260,270 A basement membrane surrounds
clusters of cells that have complex lateral interdigitations
with numerous desmosomes.260,270
The differential diagnosis of high-grade tubulopapillary
carcinoma histology in the testicular mediastinum includes
rete testis carcinoma, papillary serous carcinoma, malignant
mesothelioma, metastatic adenocarcinoma, and epididymal
carcinoma (Box 13-4). Nochomovitz and Orenstein concluded that many cystic tumors reported as rete carcinomas
actually represented serous tumors of low malignant potential or serous carcinomas.259,260,272–274 The site of origin is different for the two tumor types, with serous tumors arising in
the groove between the testis and epididymis and rete carcinomas arising in the testicular hilus.259,260,275 Both the clinical
presentation and the histologic features of mesothelioma may
mimic rete testis carcinoma.259,260 The tumor location is helpful in making the diagnosis. Mesotheliomas typically involve
the tunica vaginalis and do not involve or replace the rete testis. The use of immunohistochemistry in the differential diagnosis has been described above. Metastatic carcinoma should
especially be considered if tumors are bilateral, multinodular,
or have lymphatic/vascular space invasion or an interstitial
growth pattern. Sex cord stromal tumors of the testis can
rarely mimic rete testis carcinomas.259,260,276,277
Carcinomas of the rete testis have a poor prognosis. Only
37% of patients have been free of disease at last clinical
follow-up,259 and the mean survival is 8 months after diagnosis of the tumor.260 A few patients have experienced longer
Box 13-4 l DIFFERENTIAL DIAGNOSIS OF
TUBULOPAPILLARY NEOPLASMS OF THE
PARATESTIS*
Rete testis adenocarcinoma
Epididymal carcinoma
Malignant mesothelioma arising from the tunica vaginalis
Ovarian-type (serous, endometrioid or clear cell) carcinomas
Metastatic adenocarcinoma
*Redrawn and modified from Amin MB. Selected other problematic
testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial lesions and secondary tumors. Mod Pathol
2005;18:S131–S145, with permission.
10/11/2013 11:43:34 AM
Chapter 13 n Pathology of the Paratesticular Region 829 survival, but those patients had cystic tumors that may have
actually represented serous tumors of low malignant potential.259 Rete testis carcinomas typically spread locally and
metastasize to the para-aortic and iliac lymph nodes as well
as hematogenously to the lungs.278 The inguinal lymph nodes
may also be affected. Early diagnosis offers the best chance
for favorable outcome. Most patients who die of disease have
advanced-stage disease at the time of diagnosis. Treatment is
primarily surgical; chemotherapy and radiation have been of
limited value in the therapy of these tumors.259
Carcinoma of the Epididymis
Epididymal carcinoma is a rare tumor. It has occurred in
adults between 22 and 82 years of age; the average patient
age has been 47 years.227,279,280 Patients have presented with
scrotal masses either with or without pain. Approximately
half of the patients have had associated hydroceles.280 None
have been associated with von Hippel-Lindau disease.
Gross examination of epididymal carcinomas shows solid
and cystic gray-white tumor with areas of hemorrhage and
necrosis.280 Tumors have ranged from <1 cm281 to 14 cm
in diameter.280,282 The tumor typically obliterates part or all
of the epididymis with at most limited involvement of the
testis.280 The spermatic cord and tunica vaginalis may be
involved by tumor.
Microscopic examination reveals adenocarcinoma containing invasive glands, tubules, and papillary aggregates of
tumor cells that have clear cytoplasm containing glycogen,
at least focally (Fig. 13-23).279,280 Moderate nuclear atypia is
present, although more anaplastic, pleomorphic nuclei may
also occur. Cysts and intracystic papillary structures may
be present. In some cases, the appearance is reminiscent of
endometrioid carcinoma.21,280 Squamous differentiation may
be admixed with the adenocarcinoma, and pure squamous
carcinoma of the epididymis has been reported.280
F i g u r e 1 3 - 2 3 n Adenocarcinoma of epididymis. Note
i­nfiltrating adenocarcinoma between epididymal tubules. (Image
courtesy of Dr Steven Shen, Houston, TX.)
Amin9780781782814_ch13.indd 829
PAS stains highlight the glycogen present in tumor cells.
Mucin stains are negative.280 Immunohistochemical stains
are positive for cytokeratin and EMA; the latter stains the
luminal surface of the cytoplasm.280 Studies have yielded
conflicting results regarding CEA staining.280 Electron
microscopy shows characteristics of adenocarcinoma.280
The differential diagnosis of epididymal carcinoma includes
clear cell papillary cystadenoma. In contrast to benign neoplasms, adenocarcinomas are infiltrating and destructive
tumors that display hemorrhage, necrosis, nuclear atypia, and
mitotic activity. Adenomatoid tumors are smaller and more
circumscribed tumors that are composed of tubules lined by
flattened cells. Adenomas of the rete testis enter the differential diagnosis, but they do not involve the epididymis proper
and they do not display nuclear atypia and mitotic figures.
Epididymal adenocarcinoma also needs to be distinguished
from mesothelioma of the tunica vaginalis,283 papillary serous
carcinoma,274 and adenocarcinoma of the rete testis.259,260
Clear cytoplasm, seen in epididymal adenocarcinoma, is not a
typical feature of rete carcinomas. Serous carcinomas display
more epithelial budding, papillary structures surrounded by
desmoplastic stroma, and psammoma bodies than epididymal
carcinoma. Mesothelioma is a more diffuse process than epididymal carcinoma and often is associated with hydrocele and
tumor nucleolus along the tunica vaginalis.
The number of reported cases of primary epididymal
adenocarcinoma has been small, but it appears that about
50% of patients with this neoplasm eventually die with metastatic disease.21,280,284 This tumor usually metastasizes via
lymphatic channels to the retroperitoneal lymph nodes,280
but inguinal lymph nodes may also be involved by tumor.
Metastatic disease has also been reported in the right paraureteral area and the lung.280
Borderline and Malignant Ovarian-Type
Epithelial Tumors
Borderline and malignant ovarian-type epithelial tumors
occur infrequently in the paratesticular region, and they are
identical to their more frequent counterparts in the ovary.
Most of these tumors in the paratesticular region are serous
tumors of low malignant potential,18,285–289 but serous carcinomas,274 Brenner tumors,257,290,291 mucinous tumors,253,292,293
endometrioid tumors,288 and clear cell carcinomas294 have
also been reported in this location (Box 13-5).
These neoplasms may arise from müllerian metaplasia
of the peritoneal surface of the tunica vaginalis in a process similar to that of primary peritoneal serous tumors
in women. Many of these tumors are centered in the
epididymal–­testicular groove.274,291,292 That location suggests
origin from the appendix testis.286 It is a müllerian remnant,
and other müllerian remnants also exist in the paratesticular region.51,273,295 Some ovarian-type epithelial tumors have
been located in the spermatic cord.296
Serous tumors of low malignant potential typically
occur in midlife. The median age for borderline serous
10/11/2013 11:43:35 AM
830 Urological Pathology
Box 13-5 l HISTOLOGIC SPECTRUM
OF OVARIAN-TYPE TUMORS*
Serous neoplasms
Benign serous cystadenoma
Borderline serous tumor
Borderline tumor with microinvasion
Serous carcinoma
Mucinous neoplasms
Benign mucinous cystadenoma
Borderline mucinous tumor
Mucinous carcinoma
Clear cell adenocarcinoma
Endometrioid adenocarcinoma
Brenner tumors
Benign Brenner tumor
Malignant Brenner tumor
*Modified from Amin MB. Selected other problematic testicular and
paratesticular lesions: rete testis neoplasms and pseudotumors,
mesothelial lesions and secondary tumors. Mod Pathol 2005;18:
S131–S145, with permission.
tumors in the paratestis is 54 years, with an average age of
49 years.272,273,285,286,288,295,297 Paratesticular serous carcinomas occur mainly in younger adults with a mean age of 31
years.274 One case of paratesticular papillary serous cystadenocarcinoma has been reported in a child,298 and one was
recently reported in an 87-year-old man.299 Two cases of
malignant ovarian-type epithelial tumor have been reported
in men who received hormonal therapy for prostate carcinoma; they included an endometrioid carcinoma and a mixed
endometrioid and smooth muscle tumor.5,286,288
Presenting symptoms include scrotal enlargement and
palpable masses that may be painless or associated with discomfort. There may be an associated hydrocele.293
Serous and mucinous tumors of low malignant potential
have pink-tan, smooth outer surfaces. Cut sections reveal
variable numbers of cysts255 that contain watery or thick,
mucoid material300 and papillary excrescences.292 In contrast
to borderline tumors, carcinomas have a solid gray-tan tissue component that is not well demarcated from surrounding
structures.274
Histologic features of ovarian-type epithelial tumors are
identical to tumors of the same type seen more commonly in
the ovaries. Borderline serous tumors typically display papillary connective tissue fronds with a hierarchical branching architecture. The lining epithelium shows stratification,
tufting, nuclear atypia, and mitotic figures. Borderline
tumors do not display invasion into the surrounding stroma,
in contrast to serous carcinomas. Stromal invasion is the
characteristic that defines serous carcinoma and separates
carcinoma from borderline tumors. Stromal invasion may
be recognized by a desmoplastic stromal response, a solid
growth pattern, or isolated papillary structures surrounded
by clear spaces (Fig. 13-24). Some tumors may be predominantly borderline serous tumors with only small foci of
invasive tumor.274,287
F i g u r e 1 3 - 2 4 n Ovarian-type serous papillary tumor of paratestis. Gross appearance of a serous papillary ­cystic tumor of borderline
malignancy (A). Intracystic growth with papillae demonstrating hierarchical branching (B). Serous carcinoma with tubulopapillary architecture and psammomatous calcification (C). (Reprinted from Amin MB.
Selected other problematic testicular and paratesticular lesions: rete
testis neoplasms and pseudotumors, mesothelial lesions and secondary
tumors. Mod Pathol 2005;18:S131–S145, with permission.)
Amin9780781782814_ch13.indd 830
10/11/2013 11:43:37 AM
Chapter 13 n Pathology of the Paratesticular Region 831 F i g u r e 1 3 - 2 5 n Ovarian-type paratesticular/testicular mucinous tumor. Cystadenoma h­ istology with lining by endocervical-like
cells (A). Testicular mucinous tumor of borderline malignancy with mucin extravasation (B). (Case courtesy of Dr Thomas Ulbright,
Indianapolis, IN, USA; Reprinted from Amin MB. Selected other problematic testicular and paratesticular lesions: rete testis neoplasms and
pseudotumors, mesothelial lesions and secondary tumors. Mod Pathol 2005;18:S131–S145, with permission.)
In contrast to the single layer of bland epithelium seen
in mucinous cystadenomas, the presence of endocervical or enteric-type epithelium with stratification, tufting,
atypia and mitotic figures is diagnostic of a borderline
mucinous tumor (Fig. 13-25). Borderline mucinous tumors
do not display destructive stromal invasion. Two mucinous
borderline tumors and one mucinous carcinoma have been
recently reported in the paratesticular region.253 The paratesticular mucinous carcinoma appeared as a thickening
of the tunica vaginalis on gross examination. Destructive
stromal invasion in mucinous tumors is indicative of
carcinoma.
Endometrioid and clear cell tumors have been reported
rarely in the paratesticular region.40 Endometrioid tumors
are reminiscent of endometrial carcinoma. Clear cell carcinomas display solid, glandular or papillary architecture. One
malignant Brenner tumor was associated with areas of squamous and transitional cell carcinoma.291
Immunohistochemistry is useful in the diagnosis of
­ovarian-type epithelial tumors. Tumors of müllerian derivation stain positively with antibodies to WT1. They are cytokeratin positive, and most ovarian-type epithelial tumors
display a predominance of cytokeratin 7 staining, with less
cytokeratin 20 positivity. CEA274,285,287 and CA-125 may also
be positive. Serous tumors stain positively for B72.3.
Serous tumors need to be distinguished from carcinoma
of the rete testis and malignant mesothelioma. Location of a
tumor in the testicular hilus and the rete testis is typical of
rete testis carcinomas. Rete carcinomas also typically display a greater degree of cytologic atypia and a more solid
growth pattern than the well-defined papillary fronds seen
in serous tumors. Psammoma bodies may occur in both
serous tumors and carcinoma of the rete testis.269 Both
serous tumors and malignant mesotheliomas display papillary architecture. Serous carcinoma displays more tufting
and stratification than is typically seen in mesotheliomas.
Amin9780781782814_ch13.indd 831
Immunohistochemistry is quite useful in distinguishing the
two neoplasms (Box 13-3). Papillary serous tumors are positive for Leu M1, B72.3, and WT1. Mesotheliomas are positive for WT1, CK5/6 and calretinin and negative for Leu M1
and B72.3. The possibility of metastatic carcinoma should
be excluded when considering a diagnosis of endometrioid,
mucinous, or clear cell tumors of the paratesticular region.
Bilateral tumors and prominent lymphatic or vascular space
involvement supports a metastatic lesion. The majority of
paratesticular ovarian-type epithelial tumors present with
disease limited to the paratestis, in contrast to advancedstage disease associated with tumors metastatic to the paratesticular region.
There is very limited experience with müllerian-type
tumors of the paratesticular region. Completely excised borderline tumors have a good prognosis; no case has recurred
or metastasized after radical orchiectomy.289 Nistal reported
that mucinous tumors of the paratestis are locally aggressive tumors with little metastatic potential.293 Two patients
reported to have mucinous cystadenocarcinomas292,293 were
alive without disease after 2 years, but other authors do
not think these tumors were actually invasive.40 The single
patient reported to have a malignant Brenner tumor had a
metastasis to retroperitoneal lymph nodes at the time of
diagnosis, but he was alive without disease 1 year later.291
Complete surgical excision of ovarian-type epithelial tumors
of the paratestis is recommended.40 Adjuvant therapy should
only be considered for patients whose tumors represent
carcinoma.40
Ovarian serous borderline tumors with microscopic foci
of invasion have a prognosis similar to that of tumors of
low malignant potential, but the significance of very small
foci of invasive tumor in the paratesticular region has not
been determined. One man with a serous borderline tumor
with “focal” invasion was disease-free 1 year after surgical excision.287 A different patient reported to have focal
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832 Urological Pathology
invasion had diffuse abdominal recurrent ­disease 7 years
after surgery.274 Some authors40 believe that microinvasion
measuring <3 mm is associated with a good prognosis, but
no actual data from paratesticular tumors exist to confirm
this impression. At least one reported case of a testicular borderline serous tumor with microinvasion by criteria used for ovarian tumors has been clinically malignant,
indicating that additional experience with these lesions is
necessary before drawing conclusions about the prognostic significance of microinvasive foci.200 Thorough sampling of borderline tumors should be performed. Patients
with larger amounts of invasive serous carcinoma are
at risk for recurrent or metastatic disease.274 The role of
retroperitoneal lymph node dissection in this context is
unclear.
Mesothelial Neoplasms
Benign Mesothelial Tumors
Adenomatoid Tumor
Adenomatoid tumors are the most common mesothelial
tumors of the paratesticular region. Srigley and Hartwick
reported 23 cases,18 and Mostofi and Price149 found that
these tumors represent about one-third of all tumors in the
paratesticular region. While most paratesticular adenomatoid tumors occur in the head of the epididymis,301,302
some are seen in the tunica albuginea, spermatic cord,
and tunica vaginalis.284,301,303–307 Patients range in age from
18 to 79 years, but the lesion is seen most commonly in
the fourth decade of life. Adenomatoid tumors are usually
asymptomatic lesions that are discovered during physical examinations or in the course of other procedures.
However, if infarction occurs due to torsion, patients may
present with pain.308
Adenomatoid tumors are well-circumscribed, firm
tan, gray or white nodules that may be as large as 5 cm,
although most measure <2 cm (Fig. 13-26A). Microscopic
examination displays a plexiform pattern of nests, cords,
and tubules composed of cells with moderate to abundant
eosinophilic cytoplasm containing vacuoles (Fig. 13-26B).
The cytoplasmic vacuoles represent an important clue to
the diagnosis. Coalescence of the vacuoles gives rise to
tubular spaces. Attenuated extensions of cytoplasm called
“thread-like bridging strands” are often seen crossing these
tubular spaces.309 Nuclei are round and uniform. Mitoses
are rare. The tubules are surrounded by fibrous stroma that
may contain smooth muscle cells. Occasionally, smooth
muscle cells may be admixed with the larger, epithelioid
cells to form an adenomatoid leiomyoma.310,311 Rarely, the
tumor may infiltrate the testis312,313 and it may masquerade as a testicular neoplasm. Brenner tumors occasionally occur in association with adenomatoid tumors of the
paratesticular region.257 Necrosis is a rare occurrence in
adenomatoid tumors and is presumably due to infarction.308 Some cases have been associated with rete testis
hyperplasia.308
While the typical pattern of adenomatoid tumor results
in a straightforward “pattern recognition” diagnosis, there
are variants of this tumor that may be more challenging to
pathologists200,314 (Box 13-6). Adenoid, angiomatoid, cystic,
glandular, solid, tubular, oncocytic, and ischemic patterns
may be seen.314 Signet ring cells resulting from cytoplasmic
vacuoles may mimic the appearance of metastatic adenocarcinoma. Vacuolated cells may suggest liposarcoma or
vascular neoplasms, and the combination of vacuolated
cells with gland-like tubules can mimic yolk sac tumor or
Sertoli cell tumor. Nests or solid areas of eosinophilic cells
can suggest variants of Leydig cell tumor. Awareness that
smooth muscle cells may be admixed with the tubules of
adenomatoid tumor will prevent an erroneous diagnosis of
leiomyoma. Although adenomatoid tumors are grossly wellcircumscribed, some infiltration of surrounding muscle may
be seen at the edges of the lesion. Muscle infiltration and
any atypia resulting from reaction to infarction need to be
F i g u r e 1 3 - 2 6 n Adenomatoid tumor. A: Gross photograph of bisected testis. Note circumscribed white-yellow nodule with a hilar
epicenter. B: Microscopically, these tumors display cords and tubules composed of cells with moderate to abundant eosinophilic cytoplasm
containing vacuoles.
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Chapter 13 n Pathology of the Paratesticular Region 833 Box 13-6 l DIAGNOSTIC PROBLEMS AND
DIFFERENTIAL DIAGNOSIS OF ADENOMATOID
TUMOR*
Histologic Pattern
Differential Diagnosis
Signet ring cells
Vacuolated cells
Metastatic carcinoma
Liposarcoma
Vascular neoplasm
Yolk sac tumor
Metastatic carcinoma
Sertoli cell tumor
Leydig cell tumor
Large cell calcifying
Sertoli cell tumor
Leiomyoma
Vacuolated cells and gland-like
tubules
Nests/solid areas of eosinophilic
cells
Prominent smooth muscle
component
Infiltration of testicular
parenchyma
Infarction with atypia
Mesothelioma
Mesothelioma
*Redrawn and modified from Amin MB. Selected other problematic
testicular and paratesticular lesions: rete testis neoplasms and pseudotumors, mesothelial lesions and secondary tumors. Mod Pathol
2005;18:S131–S145, with permission.
carefully evaluated in view of the low-power architecture
and gross appearance of the tumor because they can be suggestive of mesothelioma to observers not familiar with their
occurrence.
Frozen section diagnosis of adenomatoid tumor may
be crucial in steering therapy toward a conservative resection. The gross appearance of a white circumscribed nodule
is helpful in achieving the correct intraoperative diagnosis. Appreciation of the pattern of anastomosing tubules
and cytoplasmic vacuolation are important diagnostic factors, even if some solid areas, signet ring cells, or admixed
smooth muscle are identified microscopically. The absence
of nuclear atypia or mitotic activity is helpful at the time of
frozen section, but the gross appearance of the lesion and the
low-power pattern of tubules and vacuolated cells are keys to
the correct diagnosis.
Immunohistochemical stains are useful in diagnosing
adenomatoid tumors. These neoplasms are positive for cytokeratin and epithelial membrane antigen and negative for
vimentin, carcinoembryonic antigen, and vascular markers.
A recent study emphasized the value of a positive D2-40
stain for adenomatoid tumors of the genital tract.314 Electron
microscopy demonstrates the long, slender microvilli seen in
mesothelial lesions.315,316
Adenomatoid tumors are benign lesions that should be
conservatively excised. The differential diagnosis includes
vascular lesions and malignant mesothelioma (Box 13-6).
Immunohistochemical stains and electron microscopy315,317,318
confirm the mesothelial nature of the tumor. Adenomatoid
tumors may be infiltrative, but they do not show the papillary
architecture and cytologic atypia characteristic of malignant
mesotheliomas. Furthermore, the cytoplasmic vacuoles
characteristic of adenomatoid tumors are not a feature of
malignant mesotheliomas.
Amin9780781782814_ch13.indd 833
Well-Differentiated Papillary Mesothelioma
and Meso­thelial Tumors of Uncertain Malignant
Potential
Well-differentiated papillary mesotheliomas are usually
seen in the peritoneum of young women,319 but a few cases
have been reported in the tunica vaginalis of men.149,320–322
They are rare paratesticular tumors.322 Most occur in the
second or third decade of life in men who present with unilateral or recurrent hydroceles.149,321,322 This tumor has not
been shown to be associated with asbestos exposure.
Gross examination of these lesions shows single or multiple
nodules of tumor studding a hydrocele sac. Microscopic examination reveals papillae and tubules that are lined by a single
layer of flattened to cuboidal mesothelial cells that do not contain glycogen or mucin.320,322 Solid aggregates of mesothelial
cells with luminal spaces may also be present. Mitoses are rare
or absent, and cytologic atypia is not a feature of this neoplasm.
Psammoma bodies may be seen. Fibrosis can cause some
irregular architecture that should not be mistaken for invasive
tumor.321 Immunohistochemical stains performed in a small
number of cases have shown cytokeratin and epithelial membrane antigen positivity in these neoplasms.321 Electron microscopy displays epithelial cells containing mitochondria and
rough endoplasmic reticulum; an adjacent basement membrane
is present. Luminal spaces contain short microvilli. Nuclear
p53 protein accumulation was demonstrated in one case that
had benign histology and an uneventful 3-year follow-up.323
The differential diagnosis of well-differentiated papillary mesothelioma includes reactive mesothelial hyperplasia,
malignant mesothelioma, and papillary carcinoma of the paratesticular region. Well-differentiated papillary ­mesothelioma
is a larger and more complex lesion than papillary mesothelial hyperplasia. Malignant mesotheliomas and carcinomas
of the paratestis characteristically have significant cytologic
atypia, mitotic activity, and invasive patterns that are not seen
in well-differentiated papillary mesotheliomas. Malignant
mesotheliomas may contain noninvasive areas that are indistinguishable from well-differentiated papillary mesothelioma,
so it is essential that the lesion be thoroughly sampled. Welldifferentiated papillary mesothelioma may represent a noninvasive stage of malignant mesothelioma, and complete
excision is necessary. Recurrent disease has not been reported,
but most cases reported do not have long follow-up,320–322,324 so
careful follow-up of patients is essential.
Eight cases of mesothelioma of the tunica vaginalis of
uncertain malignant potential have been recently reported.325
These neoplasms had papillary and tubulopapillary architecture similar to well-differentiated papillary mesotheliomas,
but they also displayed more complex cribriform and condensed architecture. None of the neoplasms demonstrated
any areas of invasive tumor. An average of 2.1 mitotic figures/50 HPF was seen in most of the neoplasms. Only rare
cells stained for Ki-67 and p53, and only one case stained
positively for GLUT-1. Five patients had follow-up data.
Three were alive 2, 3, and 9 years after diagnosis, and two
other patients died of unknown causes. Survival was much
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834 Urological Pathology
better than that associated with malignant mesotheliomas,
although additional studies of these neoplasms are needed to
define their biologic behavior.
Malignant Mesothelial Neoplasms
Malignant Mesothelioma
Malignant mesothelioma is the most common malignant
neoplasm of the paratesticular region that displays an epithelial growth pattern. Individual case reports and small series
of these tumors have been reported. Most arise in the tunica
vaginalis testis, but they may also be seen in the epididymis
and spermatic cord. Patients have ranged in age from 6 to 91
years. The highest incidence of this tumor has been in men
between 55 and 75 years of age. A recent study reported a
mean age of 60 years for this neoplasm.326 However, 10% of
cases reported have been in patients younger than 25 years
of age,283,327 so these neoplasms need to be considered in
the diagnosis of paratesticular masses and hydroceles, even
in pediatric patients. The only known risk factor for malignant mesothelioma of the paratesticular region is asbestos
exposure. Up to one-third of patients with this lesion have a
history of asbestos exposure, but the prevalence of asbestos
exposure is probably higher than reported due to a lack of
clinical information in many reported cases.
Most men present with either unilateral testicular
enlargement, a hydrocele that develops over the period of
several months, or a recurrent hydrocele. Rare patients have
presented with metastatic disease.328,329 Malignant mesothelioma involves the left and right paratesticular regions with
equal frequency. Rare patients may present with symptoms
of advanced disease such as scrotal nodules329 or spinal
metastases.328
Ultrasound or CT scans with or without cytology may suggest a preoperative diagnosis of malignant mesothelioma.330
Ultrasound shows a hypoechoic hydrocele with hyperechoic
peripheral masses ranging from 2 to 20 mm in size.331 These
studies are very useful in determining surgical therapy
because there is a high rate of recurrence if a local resection
is performed instead of the indicated inguinal orchiectomy.
Malignant mesothelioma most characteristically consists
of multiple firm, white nodules with papillary excrescences
on the surface of a hydrocele sac.144,283,332 The nodules or papillary areas may range from very small to 2 cm. The fluid in the
hydrocele may be clear or hemorrhagic. The tunica vaginalis
may also be thickened and studded with firm, white, plaquelike lesions. A few tumors consist of single well-circumscribed
masses between 2.5 and 7.8 cm in diameter.333
Paratesticular malignant mesotheliomas may display
epithelial (60% to 70%) (Fig. 13-27A), sarcomatous (rare),
or biphasic (30% to 40%) patterns.144 No desmoplastic
mesotheliomas have been reported in this site. Some well-­
differentiated, epithelial paratesticular mesotheliomas display
papillary structures containing fibrous tissue cores covered
with cuboidal mesothelial cells with little nuclear atypia.
The presence of slight atypia, a low mitotic rate, and tubules
invading the wall of the hydrocele sac are clues to the malignant nature in these well-differentiated neoplasms. More
commonly, malignant mesothelioma displays a tubulopapillary pattern that includes both exophytic papillary structures
and invasive tubules and papillae. The arborizing papillae
are covered by multiple layers of atypical mesothelial cells
with moderate amounts of cytoplasm and large, vesicular
nuclei that contain moderate-sized nucleoli. Solid areas of
highly atypical cells and foci of necrosis may be present,
especially in high-grade tumors. Tubulopapillary and solid
mesotheliomas have mitotic rates varying from low to very
high, with higher mitotic rates occurring in more poorly
differentiated tumors. Areas of mesothelioma in situ may
sometimes be present in the tunica adjacent to the invasive
F i g u r e 1 3 - 2 7 n Malignant mesothelioma. A: This tumor displays a tubular, papillary and solid pattern. Atypical rete tubule epithelium (left) is associated with the invasive neoplasm. B: A calretinin stain is positive. This stain is useful in distinguishing mesothelioma from
serous carcinoma in the paratesticular region.
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Chapter 13 n Pathology of the Paratesticular Region 835 mesothelioma. A transition from benign mesothelium to
mesothelioma in situ to invasive malignant mesothelioma
may be demonstrable.
Biphasic malignant mesothelioma consists of an admixture of tubulopapillary elements with a spindle cell sarcomatous stroma arranged in fascicles or a storiform pattern
resembling malignant fibrous histiocytoma. The degree of
atypia in the stroma is variable. Some tumors contain uniform, mildly atypical spindle cells, whereas others display
a great deal of nuclear pleomorphism, numerous mitoses,
and areas of necrosis. One case had metaplastic osseous and
chondroid differentiation of the stroma, and these ­stromal
elements were attributed to metaplasia of the ­stromal cells.334
The only reported case of a sarcomatous mesothelioma
of the paratesticular region occurred in a 32-year-old man
with no history of asbestos exposure.335 The tumor ­displayed
spindle and polygonal cells containing ample ­eosinophilic
cytoplasm and oval, vesicular nuclei with prominent nucleoli and numerous mitotic figures. Some cells at the edge
of the tumor had cytoplasmic vacuoles that contained
­hyaluronidase-sensitive Alcian blue material. No microvilli
were identified on ultrastructural examination of this sarcomatous mesothelioma.
Immunohistochemical studies of malignant mesothelioma have shown positive staining for CK5/6, WT-1, and
calretinin (Fig. 13-27B).336,337 Negative stains include CEA,
Leu-M1, Ber EP4, B72.3, and E-cadherin. Some biphasic
mesotheliomas have displayed cytokeratin staining of the
spindle cell component of the neoplasms.144 Some authors
have reported that a negative E-cadherin stain coupled
with a positive calretinin stain is helpful in the diagnosis
of mesothelioma.337 Some mesothelioma markers may overlap with immunohistochemical markers of other tumors in
the differential diagnosis of mesothelioma. WT-1 is positive in both mesothelioma and papillary serous carcinoma.
Calretinin is positive in mesothelioma, carcinoma of the
rete testis, and epididymal carcinoma. Therefore, a panel
of immunostains is useful in eliminating other neoplasms
from the differential diagnosis of malignant mesothelioma
(Table 13-2).
Ultrastructural study of mesothelioma326,338–340 displays
long, branching microvilli, abundant cytoplasmic fibrils,
desmosomes, and sparse intracellular organelles. These features are the same as those seen in malignant mesotheliomas
at other sites.
The differential diagnosis of malignant mesothelioma of
the paratesticular region includes mesothelial hyperplasia,
well-differentiated papillary mesothelioma, paratesticular
müllerian-type tumors, adenocarcinoma of the rete testis,
adenocarcinoma of the epididymis, adenomatoid tumor,
and metastatic carcinoma. The differential diagnoses of
malignant mesothelioma compared to mesothelial hyperplasia, adenomatoid tumor, well-differentiated papillary mesothelioma, and paratesticular serous carcinomas have been
discussed. Distinction of paratesticular malignant mesothelioma from rete testis adenocarcinoma may be difficult. The
latter tumor is located at the testicular hilum and displays
Amin9780781782814_ch13.indd 835
Table 13-2 n DIFFERENTIAL DIAGNOSIS OF
HIGH-GRADE TUBULOPAPILLARY NEOPLASMS
IN THE RETE TESTIS*
Malignant
mesothelioma
Papillary serous
carcinoma
Other
Rete testis or
epididymal
carcinoma
Metastatic
carcinoma
WT-1 and other
Mesothelial markers (calretinin, CK56)
positive
Adenocarcinoma related markers
negative (BerEP4, B72.3, E-cadherin)
Adenocarcinoma-related markers
positive
Mesothelioma markers negative
WT-1 and CA 125 positive
Psammoma bodies may be present
Adenocarcinoma markers positive
Mesothelioma markers negative
WT-1 positive
CA 125 negative
No primary tumor elsewhere
Areas of transition from normal
structures
CD10 positive
Calretinin ±
History of primary tumor in other
location
Bilateral tumor
Vascular and lymphatic space invasion
Interstitial growth between normal
glandular structures
Perform immunostains for unknown
primary tumor
*Modified from Amin MB. Selected other problematic testicular and
paratesticular lesions: rete testis neoplasms and pseudotumors,
mesothelial lesions and secondary tumors. Mod Pathol 2005;18:
S131–S145, with permission.
a transition from rete adenocarcinoma in situ to invasive
neoplasm.341 Epididymal adenocarcinomas are centered in
the epididymis and not usually associated with a hydrocele.280 Furthermore, they are often composed of epithelial
cells that display clear cytoplasm, at least focally. A history
of prior neoplasms is helpful in distinguishing malignant
mesothelioma from metastatic carcinoma in the paratesticular region.
Malignant mesotheliomas are aggressive tumors with
high recurrence rates. The median time to tumor recurrence
is 10.5 months.332 More than half of the patients reported
developed recurrences and/or metastatic tumor. Thirty-nine
percent have had local recurrences, 56% have had inguinal,
retroperitoneal, or cervical lymph node metastases, and 65%
developed lung, mediastinal, bone,328 or brain307 metastases. Only one-third of reported patients were alive without
disease at last follow-up. Univariate analysis showed that
patients younger than age 60 and those with organ-confined
disease332 have longer survival than other patients.
The optimal treatment for paratesticular malignant mesothelioma is radical inguinal orchiectomy.332 Limited local
resection should be avoided due to the high frequency of
local recurrence.332 Some investigators have recommended
that retroperitoneal lymph node dissection or postoperative radiation therapy should be performed.342 The value of
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836 Urological Pathology
Box 13-7 l BENIGN MESENCHYMAL TUMORS
OF THE PARATESTICULAR REGION
Common (90%)
Lipoma or lipomatous hyperplasia
Includes variants (angiolipoma, vascular myxolipoma,
myolipoma)
Rare (10%)
Leiomyoma
Includes epithelioid and myxoid types
Angiomyofibroblastoma
Includes cellular angiofibroma and
a­ ngiomyofibroblastoma-like tumor
Angiomyxoma
Schwannoma
Rhabdomyoma
Hemangioma
Neurofibroma
Granular cell tumor
Other rare tumors
adjuvant chemotherapy and radiation therapy is not clear
at this time, although recent randomized trials have shown
significant improvement in time to progression and survival
with chemotherapy for malignant mesothelioma.343
Mesenchymal Neoplasms
The incidence of paratesticular soft tissue tumors is difficult to determine.284,344–346 Benign and malignant soft tissue tumors represented 52% of all paratesticular tumors
in the Canadian Reference Center for Cancer Pathology
cases.18 About 70% of paratesticular tumors reported have
been benign (Box 13-7) and 30% have been malignant
(Box 13-8).347 The proportion of benign mesenchymal
tumors, especially lipomas, may be considerably >30% since
most of these tumors are not referred for consultation.
Benign Mesenchymal Tumors
The most common soft tissue tumors of the paratesticular
region are lipomas and leiomyomas. Lipomas account for
90% of the soft tissue tumors in this area. Some paratesticular
Box 13-8 l MALIGNANT MESENCHYMAL
TUMORS OF THE PARATESTIS
Most Frequent
Liposarcoma
Leiomyosarcoma
Rhabdomyosarcoma
Malignant fibrous histiocytoma
Rare
Osteosarcoma
Malignant mesenchymoma
Epithelioid sarcoma
Synovial sarcoma
Extraskeletal myxoid sarcoma
Others
Amin9780781782814_ch13.indd 836
lipomas may actually represent lipomatous hyperplasia
rather than true neoplasms. Variants of lipoma, including
angiolipoma, vascular myxolipoma, and myolipoma also
occur in the paratestis.284,348 These lipoma variants are distinguished from liposarcomas by the lack of cytologic atypia,
lipoblasts, or a plexiform capillary network in the lipomas.
Leiomyomas may have epithelioid or myxoid patterns.349
Other benign mesenchymal tumors of the paratesticular
region include schwannoma, neurofibroma, hemangioma,
rhabdomyoma, and granular cell tumor.
Aggressive Angiomyxoma
Aggressive angiomyxoma was originally described in the pelvic soft tissue of women,350 but it is now known to occur in the
spermatic cord in both adults and children.351–353 These tumors
are locally infiltrative and therefore characterized by disease
recurrences, but they do not metastasize. They are often large at
the time of diagnosis. They typically appear to be well-circumscribed and myxoid on gross examination. Aggressive angiomyxomas are not encapsulated, and microscopic examination
shows small nests and tongues of the lesion extend beyond the
grossly apparent edge of the neoplasm. Microscopically, these
lesions have a background of hypocellular stroma containing
blood vessels of variable size. Prominent large dilated blood
vessel walls usually contain smooth muscle. Some vessel
walls are typically hyalinized. Cellularity may be increased
around blood vessels. Foci of hemorrhage may be present.
The tumor stroma is myxoid and contains collagen as well as
bland spindle and stellate cells with oval round to oval nuclei,
no nuclear atypia and no more than a very rare mitotic figure.
Some angiomyxomas have microscopic features that overlap
with angiomyofibroblastomas.
The rate of recurrence of aggressive angiomyxoma in the
paratestis (20%) is lower than that seen in women354 because
lesions of the paratestis are easier to completely resect.
The recommended therapy is wide resection with careful
follow-up.354
Angiomyofibroblastoma (Synonym: Also
Called Angiomyofibroblastoma-Like Lesions;
Cellular Angiofibroma)
Like angiomyxoma, angiomyofibroblastoma is most commonly seen in the soft tissue of the female pelvis, especially
vulva.355 Some cases do occur in the inguinal region and scrotum of men.356 These lesions are small, rubbery, well-circumscribed tumors. They are more cellular than angiomyxomas,
and they may contain both hypercellular and hypocellular
areas (Fig. 13-28). They display a network of blood vessels
that are smaller, less dilated, and less hyalinized than those
seen in angiomyxomas. Stromal cells are stellate or spindleshaped without atypia or significant mitotic activity. They may
aggregate and whorl around blood vessels.354 Multinucleated
stromal cells are often present. Enlarged nuclei that display
degenerative changes characterized by smudged nuclei may
be seen. Fat may be present in the stroma. Cellular angiofibroma357 and “angiomyofibroblastoma-like tumor of the male
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Chapter 13 n Pathology of the Paratesticular Region 837 F i g u r e 1 3 - 2 8 n Angiomyofibroblastoma. Note proliferation
of bland small spindle cells with a vaguely storiform growth pattern
on a background of abundant small blood vessels, some of which
have hyalinized walls.
genital tract”356 represent variants of ­angiomyofibroblastoma.
Angiomyofibroblastomas are benign neoplasms that should
be treated by local resection,354 although very rare angiomyofibroblastomas have had malignant histologic features, with
sarcomatous transformation.358
Some tumors may show features of both angiomyxoma
and angiomyofibroblastoma. Immunohistochemical stains
have been proposed as a way to separate the two entities, but
more recent studies show great overlap of the two lesions.
Both stain positively for smooth muscle actin, desmin,
CD34, and sex hormone receptors.359,360 Tumors with criteria
suggestive of both angiomyxoma and angiomyofibroblastoma should be completely resected with subsequent followup clinical examinations.354
Malignant Mesenchymal Tumors
Leiomyosarcoma, rhabdomyosarcoma, liposarcoma, malignant fibrous histiocytoma, and fibrosarcoma are the most
frequent malignant mesenchymal tumors that occur in the
paratestis.344,345,354,361–363 A recent study of adult spermatic
cord sarcomas showed that 51% were liposarcomas, 19%
were leiomyosarcomas, 13% were embryonal rhabdomyosarcomas, and 11% represented malignant fibrous histiocytomas,364 and 62% of patients had high-grade sarcomas
in that study. Between 7% and 10% of pediatric rhabdomyosarcomas occur in the paratestis.365 A rare example of a
primary spermatic cord osteosarcoma has been reported.366
One malignant mesenchymoma composed of distinct areas
of liposarcoma and leiomyosarcoma367 and one mixed liposarcoma and osteosarcoma of the spermatic cord368 have
been reported. We have seen a malignant mesenchymoma
composed of ganglioneuroblastoma and rhabdomyosarcoma. A rare case of epithelioid sarcoma arising from the
vas deferens has also been reported.369 Other rare paratesticular sarcomas include synovial sarcoma and extraskeletal myxoid chondrosarcoma.354 With the exception of
embryonal rhabdomyosarcoma, soft tissue sarcomas of
the paratesticular region are tumors of the adult population. Almost all patients with paratesticular sarcomas come
to attention because of a palpable mass in the scrotum or
inguinal area.
Rhabdomyosarcoma
The most common site for rhabdomyosarcomas is the
paratesticular region (Fig. 13-29A).354 The median age is
15 years, with a range from 7 years of age to adults. Half
of all paratesticular rhabdomyosarcomas occur in pediatric
patients. On gross examination, paratesticular rhabdomyosarcomas are infiltrating, firm, gray-white neoplasms that
may demonstrate areas of necrosis.
Embryonal rhabdomyosarcoma is the most common type
of rhabdomyosarcoma in the paratestis, although any type
may occur in this region.370 Embryonal rhabdomyosarcomas
are very cellular small round blue cell tumors. There are
also variable numbers of rhabdomyoblasts that have abundant eosinophilic cytoplasm (Fig. 13-29B). Strap cells with
F i g u r e 1 3 - 2 9 n Rhabdomyosarcoma. A: This paratesticular rhabdomyosarcoma is a m
­ ultilobular, fleshy white mass adjacent to the testis.
B: Embryonal rhabdomyosarcoma displays a proliferation of small, round, blue cells. Cells with more abundant, eosinophilic cytoplasm are
rhabdomyoblasts.
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838 Urological Pathology
cross-striations may be present. They often display partial
monosomy of chromosome 11.371
Sixty percent of tumors classified as the spindle cell ­variant
of embryonal rhabdomyosarcomas occur in the paratesticular
region.370 Spindle cell rhabdomyosarcomas display elongated
fusiform cells that may resemble the cells of leiomyosarcoma,
a tumor rarely seen in the paratesticular region in children.
Careful examination of spindle cell rhabdomyosarcomas
reveals cross-striations, and immunostains are also helpful in
this differential diagnosis. The spindle cell variant has a better
prognosis than other embryonal rhabdomyosarcomas,354 and
pediatric rhabdomyosarcomas have a better prognosis than
adult rhabdomyosarcomas in the paratesticular region.
Alveolar rhabdomyosarcoma is an uncommon type of
rhabdomyosarcoma seen in the paratesticular region, but
these are very aggressive tumors. Fibrous trabeculae separate the tumor cells into “alveolar” nests of primitive tumor
cells with poor cell cohesion, so that the peripheral cells
appear to adhere to the fibrous stroma. Tumor nests may
therefore appear to be solid or alveolar, with peripheral
cells lining the fibrous stroma separating tumor cell nests.
Multinucleated giant cells may be present, and cells may
display clear cytoplasm. Any amount of alveolar pattern is
sufficient to classify the tumor as an alveolar rhabdomyosarcoma for prognostic and therapeutic purposes, because this
tumor has a worse prognosis than other types of rhabdomyosarcoma. A solid variant of alveolar rhabdomyosarcoma has
been reported in this location.372 These tumors have a specific chromosome translocation t(2:13) or t(1;13) resulting
in formation of PAX-FKHR fusion genes.373 Genetic studies
may be useful in establishing the diagnosis.
The least common type of rhabdomyosarcoma to occur
in the paratesticular region is pleomorphic rhabdomyosarcoma, which is usually seen only in adult patients. The incidence of this tumor type has probably been overestimated.
Pleomorphic rhabdomyosarcoma displays a patternless
proliferation of spindle and polygonal cells with abundant
brightly eosinophilic cytoplasm, highly atypical nuclei, and
mitotic figures. Although strap-shaped cells may be present,
cross-striations are difficult to identify.374
Immunohistochemical staining of these tumors is recommended because many of the tumors formerly thought to
represent pleomorphic rhabdomyosarcoma would probably
be classified today as malignant fibrous histiocytomas.354
Antibodies to desmin are the most sensitive marker of striated muscle differentiation,375 but these antibodies are not
specific and may stain other types of sarcomas. Antibodies
to MyoD1 and myogenin are the most specific markers for
rhabdomyosarcoma.376,377 Actin stains, including those using
antibodies to smooth muscle actin, may be positive in some
rhabdomyosarcomas374,378; these stains alone do not distinguish between leiomyosarcoma and rhabdomyosarcoma.
Leiomyosarcoma
Nearly one-third of paratesticular sarcomas in adults represent leiomyosarcomas.344,345,354,361,362 Paratesticular leiomyosarcomas are typically painless scrotal masses that occur in
Amin9780781782814_ch13.indd 838
men between 34 and 86 years of age, with an average age of
62 years and a median age of 64 years.379 They are tumors of
the adult population; they are very rare in childhood. Most
of these neoplasms involve the spermatic cord or testicular
tunics, but the epididymis may also be affected.379 A recent
review of 24 primary paratesticular leiomyosarcomas found
11 tumors in the testicular tunics, 10 in the spermatic cord,
1 in the scrotal subcutis, 1 in the dartos muscle, and 1 in the
epididymis.379
Leiomyosarcomas are often well circumscribed, but some
have an infiltrative growth pattern. These tumors are firm,
gray-tan masses on gross examination. They range in size
from 2 to 9 cm. Microscopic examination of these tumors
displays features of smooth muscle differentiation, including interlacing bundles of spindle-shaped cells with bluntended nuclei. Leiomyosarcomas may resemble leiomyomas
with abnormal mitotic activity, or they may display marked
cellular and nuclear pleomorphism and areas of necrosis.
Even highly pleomorphic tumors that may resemble malignant fibrous histiocytomas usually contain some areas that
are typical of smooth muscle neoplasms. Epithelioid areas
are present in some tumors, and one paratesticular leiomyosarcoma recently studied also displayed vascular invasion.379 Necrosis is present in less than half of paratesticular
leiomyosarcomas. Scattered lymphocytes, lymphoid aggregates, and foamy macrophages are seen in some tumors.379
Myxoid stromal tissue may be present. A few sarcomas in
the paratesticular area have had components of both leiomyosarcoma and liposarcoma.380 Mitotic figures are present
in all paratesticular leiomyosarcomas; the number of mitotic
figures has ranged from <1 MF per 10 high power fields to
>70 MF/10 HPF.379 Any mitotic activity in a paratesticular
smooth muscle tumor is an indicator of a leiomyosarcoma.354
Immunohistochemistry is helpful in confirming smooth
muscle differentiation.381 Most cases stain strongly with antibodies to muscle-specific actin, smooth muscle actin, and
desmin. Some also display CD34 positivity. Focal cytokeratin and S-100 protein positivity may occur, but myogenin
stains have been negative.379 Some spindle cell rhabdomyosarcomas in children may resemble leiomyosarcomas. The
diagnosis of paratesticular leiomyosarcoma in the pediatric
age group should not be made unless immunohistochemical
stains for MyoD1 and myogenin are negative.354
The differential diagnosis of paratesticular leiomyosarcomas includes inflammatory myofibroblastic tumor. The latter
lesion may have mitotic figures, but cells have nuclei with
tapered rather than blunt ends. An inflammatory element is
often seen and cytologic atypia is not a feature of inflammatory myofibroblastic tumor. Aggressive fibromatosis occurs
in the paratestis,382 and it has a more infiltrative pattern than
seen in leiomyosarcoma. Solitary fibrous tumors383 have been
reported in the spermatic cord. They often have a hemangiopericytomatous pattern, and they lack the desmin positivity
that is characteristic of leiomyosarcomas. Careful examination and thorough sectioning of pleomorphic leiomyosarcomas in order to identify areas typical of smooth muscle
tumor is helpful in excluding other pleomorphic sarcomas
10/11/2013 11:43:46 AM
Chapter 13 n Pathology of the Paratesticular Region 839 such as dedifferentiated liposarcoma and malignant fibrous
histiocytoma.
Most low-grade leiomyosarcomas of the paratestis are
indolent neoplasms, but high-grade tumors behave aggressively. Fisher et al.379 recently showed that the grade of the
tumor correlates with clinical outcome when necrosis, mitotic
activity, and nuclear pleomorphism are considered together.
Grade 1 tumors lack necrosis, have <6 MF/10 HPF, and have
only occasional pleomorphic nuclei. Grade 2 tumors have
focal necrosis (<15%) and/or >6 MF/10 HPF or prominent
nuclear pleomorphism. Grade 3 tumors have >15% necrosis
with any degree of nuclear pleomorphism and mitotic count.
These authors found that all seven patients with grade 1 tumors
(some of whom had had tumor recurrences) and all three
patients with grade 2 tumors were alive without disease at last
follow-up. However, all four patients with grade 3 tumors died
of their disease. Complete, and even radical, resection of these
tumors is necessary for optimal results. Literature addressing adjuvant therapy after radical orchiectomy is limited and
inconclusive because these neoplasms are uncommon.
Liposarcoma
Liposarcoma is the most common malignant tumor of the
paratesticular region.354,384 Twelve percent of liposarcomas
in one study were seen in inguinal or paratesticular areas.384
Paratesticular liposarcomas are usually well-differentiated
tumors that have a prolonged clinical course. Myxoid,
round cell, and pleomorphic liposarcomas also occur in this
location.354
Paratesticular liposarcomas are detected as painless mass
lesions.385 Some are found during repair of hernias. The age
range is 41 to 87 years, with a mean age of 63 years.385 In a
recent study of paratesticular liposarcomas, tumors involved
the spermatic cord, testicular tunica, and epididymis.385
Liposarcomas often resemble fat on gross examination,
although some are firm due to fibrous tissue components
(Fig. 13-30A) and others are more myxoid than fatty. These
neoplasms range from 3 to 30 cm in diameter, with a mean
size of 11.7 cm.385 Well-differentiated liposarcomas resemble fat on gross examination, although the sclerosing variant
displays areas of dense fibrotic tissue. Any firm or solid areas
evident in a grossly fatty tumor should be carefully sectioned
in an attempt to identify foci of dedifferentiation. Myxoid
liposarcomas have a gelatinous appearance. Any firmer or
whiter nodules in the gelatinous tissue should be sectioned
because they may represent focal round cell differentiation.
Pleomorphic liposarcomas typically display areas of necrosis. While liposarcomas may appear lobulated and well circumscribed, they typically infiltrate the surrounding tissue.
All types of liposarcomas may occur in this area, but welldifferentiated sclerosing or lipoma-like liposarcomas are the
most common. Well-differentiated sclerosing liposarcoma
contains a significant component of fibrous tissue admixed
with adipocytes (Fig. 13-30B). Atypical nuclei are present
in the fat or fibrous tissue or both, but lipoblasts are rare and
do not need to be identified for the diagnosis of this subtype
of well-differentiated liposarcoma. A chronic inflammatory infiltrate may obscure part of the lesion.384 Lipoma-like
well-differentiated liposarcomas resemble mature fat, but
they contain cells with enlarged, hyperchromatic nuclei as
well as scatted lipoblasts. The term “atypical lipoma” should
not be used for these neoplasms in the paratestis because
they are associated with both a high (79%) risk of recurrence and the possibility of dedifferentiation.386 Myxoid
change may occur in well-differentiated liposarcoma,
but it lacks the plexiform vascular component seen in myxoid liposarcoma. Dedifferentiated liposarcoma is defined
as a high-grade sarcoma arising in the setting of a well-­
differentiated liposarcoma.387–389 The dedifferentiated component of the tumor displays features of malignant fibrous
histiocytoma, high-grade fibrosarcoma,387 or other types
of mesenchymal neoplasms. Dedifferentiated liposarcoma
F i g u r e 1 3 - 3 0 n Liposarcoma. A: The ill-demarcated white mass represents a dedifferentiated liposarcoma. B: Well-differentiated
sclerosing liposarcoma has atypical nuclei in a collagenous background. Lipoblasts and mitotic figures are not often identified in this type
of liposarcoma.
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840 Urological Pathology
must be distinguished from other types of high-grade
­sarcoma by the presence of coexisting well-differentiated
liposarcoma. The high-grade sarcomatous component has
a different gross appearance, with firmer fibrous-appearing
tissue, than the juxtaposed well differentiated liposarcoma.
Approximately 8% of dedifferentiated liposarcomas have
occurred in the paratesticular region.387
More than half of the well-differentiated liposarcomas in
a recent study385 recurred and dedifferentiation was noted
in some of the recurrences, but there were no metastases of
well-differentiated liposarcoma in that series except in a case
with dedifferentiation. Recurrences may occur many years
after the original tumor is excised. The prognosis of tumors
with dedifferentiation is more guarded.
Myxoid liposarcoma is less common in the paratesticular region than well-differentiated liposarcoma.390 Patients
with these tumors have soft, gelatinous tumor masses.
Micro­scopi­cally, these tumors display myxoid, lobulated
tissue with a prominent network of branching thin-walled
blood vessels. Lipoblasts are present and easily identified.
Increased cellularity is seen at the edge of tumor nodules.
Round cell liposarcoma may arise in the setting of myxoid
liposarcoma. Round cell liposarcoma is very cellular, and
contains crowded, enlarged, atypical nuclei. It lacks any
prominent vascular pattern. Both of these liposarcoma variants display the same chromosomal abnormality, t(12;16),
resulting in fusion of the CHOP gene on chromosome 12q13
with the FUS (TLS) gene on chromosome 16p11.391 Round
cell liposarcoma is diagnosed when it either exceeds 25% of
the area of the original myxoid liposarcoma or produces a
nodule in the myxoid liposarcoma.392 About 20% of patients
with paratesticular myxoid liposarcoma develop metastatic
disease,393,394 but a round cell component is predictive of an
adverse outcome.393,394
Pleomorphic liposarcoma, a variant not commonly seen
in the paratesticular region, presents as a mass that often
has necrotic areas. This tumor is very cellular, with highly
atypical, pleomorphic nuclei and numerous mitotic figures.
Pleomorphic liposarcoma may resemble malignant fibrous
histiocytoma with intermingled lipoblasts, or it may be composed of sheets of epithelioid, pleomorphic, lipoblast-like
cells.395 These are high-grade sarcomas, and associated mortality exceeds 40%.394
The differential diagnosis of well-differentiated liposarcoma of the paratestis is with benign lipomas. Cytologic
characteristics are important in the assessment of these
lesions because well-differentiated lipoma-like liposarcomas have nuclear atypia that is not seen in benign lesions
of fat. The appearance of sclerosing liposarcomas is sufficiently characteristic that is should not be confused with
other lesions. Dedifferentiated liposarcomas must be distinguished from other sarcomas by the presence of a welldifferentiated liposarcoma component. The possibility of
extension of metastasis from retroperitoneal liposarcomas
must be excluded before classifying a liposarcoma as a primary paratesticular liposarcoma.
Amin9780781782814_ch13.indd 840
Malignant Fibrous Histiocytoma
Malignant fibrous histiocytoma occurs rarely in the paratesticular area.396–398 Fewer than 20 cases have been reported
in the English literature. Most paratesticular malignant
fibrous histiocytomas occur in men over the age of 50.399
They occur as solitary mass lesions that range in size from
<1 cm to more than 20 cm.399 Nine patients in one recent
series399 had satellite tumor nodules at presentation. These
tumors are grayish-tan masses that may contain necrosis.
Microscopic examination shows intermediate- to highgrade sarcomas that usually display a storiform pattern of
spindle-shaped cells. Myxoid, giant cell, and inflammatory
variants of malignant fibrous histiocytomas are less common that the storiform type. Lin et al.399 recently reported
that 83% of paratesticular malignant fibroma histiocytomas
are of the storiform–pleomorphic type, with only a few
giant cells, inflammatory and myxoid variants. Cells are
pleomorphic, with atypical hyperchromatic nuclei, variable
numbers of mitotic figures, and sometimes an associated
inflammatory infiltrate. Tumors with a prominent inflammatory infiltrate may be misdiagnosed as inflammatory myofibroblastic tumor.
The differential diagnosis of malignant fibrous histiocytoma includes other pleomorphic sarcomas, metastatic carcinoma, and metastatic melanoma. Immunohistochemical
stains are useful in confirming the diagnosis. Tumor cells
stain positively for vimentin and CD68. Stains for cytokeratin, S-100 protein, desmin, smooth muscle actin, muscle-specific actin, CD34, epithelial membrane antigen, and
CD117 are negative. Stains for cytokeratin and melanoma
markers are useful in excluding the possibility of metastatic
carcinoma or melanoma.
Malignant fibrous histiocytoma may be diagnosed earlier in the paratesticular region than at other sites and may
therefore be associated with a better prognosis than the same
tumor at other locations,398 although retroperitoneal and
mediastinal adenopathy has been reported in some cases.400
Lin et al.399 found that tumor size does not predict clinical
progression, but satellite nodules at the time of disease presentation are an indication of early local metastasis; progression of disease was commonly associated with these satellite
nodules. Recurrence and metastasis is common for paratesticular malignant fibrous histiocytomas. The overall prognosis is poor despite adjuvant therapy.
Grading and Staging of Paratesticular Sarcomas
The American Joint Committee on Cancer staging system is
currently used in the United States.401 Paratesticular sarcomas are classified as either low-grade or high-grade sarcomas. Low-grade tumors include those classified as grade 1
in a three-tier system and those classified as grades 1 and 2
in a four-tier grading system. High-grade sarcomas are those
classified as grades 2 and 3 in a three-tier grading system
and those classified as grades 3 and 4 in a four-tier system.
All paratesticular sarcomas should be considered deep neoplasms. The TNM stage grouping takes into account the size
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Chapter 13 n Pathology of the Paratesticular Region 841 of the primary tumor, presence or absence of lymph node
and distant metastases, and tumor grade.
Treatment of Paratesticular Sarcomas
All paratesticular sarcomas should be managed by complete resection with high ligation of the spermatic cord.402–404
Inadequately resected tumors should be treated with wide inguinal reresection, including completion orchiectomy or removal
of the cord remnant to the level of the internal inguinal ring
with surrounding soft tissue and scar excision, all with negative
surgical margins.364 Large tumors, those with an inguinal location, prior transection of the tumor, and involved or close margins are associated with increased risk of local recurrence403
that may be decreased with adjuvant radiotherapy.402–404 The
question of whether a retroperitoneal lymph node dissection
should be performed is controversial,362,402–404 but no study has
shown that a prophylactic lymph node dissection is beneficial
in general. Retroperitoneal lymph node dissection has been
recommended for patients with rhabdomyosarcoma and radiographically suspicious lymph nodes.346,365,405 Adjuvant chemotherapy has been very effective in children with paratesticular
rhabdomyosarcoma,346,365 but there has not been a controlled
study of its benefit in adult patients. In other anatomic sites, it
has been shown to increase time to recurrence or metastasis at
other sites406 and to increase overall survival in patients with
high-grade sarcomas.407
Hematopoietic and Lymphoid Neoplasms
Malignant Lymphoma
Paratesticular lymphoma is usually the result of spread to
the epididymis or spermatic cord from a primary lymphoma
in the testis,408,409 although lymphoma may also spread from
other primary sites. There are only a few reported cases of
lymphoma presenting as an epididymal mass, and patient ages
have ranged the third decade to the eighth decade of life.408,410
Types of lymphoma presenting as paratesticular masses are
variable. One young patient had an extranodal marginal zone
B-cell lymphoma of the mucosa-associated lymphoid tissue
type confined to the epididymis; this patient was disease-free
36 months after surgical excision.411 Three other patients in
the third and fourth decades of life had sclerosing lymphomas
that were either partially or totally follicular and either mixed
small and large cell type or a large cell lymphoma.408,411,412
While one of these three tumors was bilateral, none had spread
beyond the epididymis. Two patients were not initially treated
because they were not recognized as lymphoma, and both
recurred.408,413 One older patient had an Epstein-Barr virus–
positive intravascular lymphoma of T-cell lineage. Although
the tumor initially presented as an epididymal tumor, disseminated tumor was later discovered. It resulted in patient death in
spite of chemotherapy.410 Two elderly patients had stage I diffuse large cell lymphomas that were treated with radiation in
one case and chemotherapy in the other case.414,415 Follow-up
was short in both cases, but one patient had developed widespread disease and died within a year of diagnosis. While the
Amin9780781782814_ch13.indd 841
number of epididymal lymphomas has been quite limited,
some authors40 have suggested that epididymal lymphomas in
young men are more likely to be low- to intermediate-grade
tumors with indolent behavior, in contrast to more aggressive
lymphomas seen in older patients.
Spermatic cord lymphoma usually represents spread from
testicular lymphoma.408 Only 13 cases of primary spermatic
cord lymphoma have been reported.408,416,417 Those patients
ranged in age from 21 to 89 years and presented with hard,
painless masses in the upper scrotum or inguinal canal. The
tumors were usually diffuse large cell lymphomas. Most
patients were treated surgically, either with or without radiation, and most developed widespread or central nervous system relapses shortly after diagnosis. Lymphomas involving
the spermatic cord behave in a manner similar to those in
the testis, and local therapy alone is not adequate treatment.
One reported case of paratesticular lymphoma involved the
tunica albuginea bilaterally.408 One adult patient presented
with right inguinoscrotal pain and swelling 7 years after
a renal transplant and died despite chemotherapy for his
aggressive posttransplant epididymal lymphoma.418
Most lymphomas of the paratesticular area have been
B-cell lymphomas, but an epididymal T-cell lymphoma410
and a case of secondary mycosis fungoides419 have been
reported in the epididymis.
Plasmacytoma
Plasmacytoma has been reported in the epididymis of
­middle-aged to elderly patients, some of whom have had
multiple myeloma.420 These tumors are composed of aggregates of plasma cells that may be atypical or immature and
express either monotypic immunoglobulins of IgG or IgA
type or light chains without heavy chains. They do not usually stain with the B-cell marker CD20 or leukocyte common
antigen, but they usually do express CD79a and (often) epithelial membrane antigen.40 Poorly differentiated tumors may
stain for epithelial membrane antigen and/or CD138 without
CD20 or CD45 staining, causing a mistaken consideration of
an epithelial tumor.40 Attention to the cytologic features and
clinical history are helpful in achieving the correct diagnosis.
Granulocytic Sarcoma
Granulocytic sarcoma is very rare in the paratesticular
region, and it usually represents disease spread from the testis.421 One 73-year-old man who presented with granulocytic
sarcoma of the epididymis with extension to the spermatic
cord later developed acute myeloid leukemia.40 This tumor
may be mistaken for lymphoma. The presence of eosinophils
in the infiltrate may be helpful in establishing the correct
diagnosis. Patients may have circulating blasts and acute
myeloid leukemia. Neoplastic myeloid cells usually stain
positively by histochemical stains for chloroacetate esterase
and by immunohistochemical stains for myeloperoxidase
and lysozyme, but not for the B- and T-cell markers seen in
lymphomas.40
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842 Urological Pathology
Other Rare Neoplasms
Melanotic Neuroectodermal Tumor of Infancy
(Synonyms: Retinal Anlage Tumor, Melanotic
Hamartoma, Melanotic Progonoma)
Melanotic neuroectodermal tumor of infancy is also known
as melanotic progonoma and retinal anlage tumor. It is rare
and is seen in children <1 year of age. Most of these tumors
occur in the head and neck.422 Several cases have been
reported in the paratesticular region, especially in the epididymis.423–425 Some authors believe that melanotic neuroectodermal tumors are dysembryogenetic neoplasms that are
always congenital.425 These tumors are of neuroectodermal
origin. They occur in young children, although one paratesticular tumor was reported in an 8-year-old child.425
The typical clinical presentation of melanotic neuroectodermal tumors is a scrotal firm mass, sometimes associated with a hydrocele, in an infant. Urinary vanillylmandelic
acid/homovanillic acid levels are elevated in some patients
and are potentially useful in detecting recurrent disease.426
Melanotic neuroectodermal tumors of infancy typically involve the epididymis. They are well-circumscribed,
blue-gray rubbery masses that measure <4 cm in diameter.
Microscopically, these tumors display two cell populations.
Cellular aggregates of tumor cells are separated by fibrous
stroma. Large, melanin-containing, columnar to cuboidal
epithelioid cells are located peripherally around nests of
smaller neuroblastic cells with scant cytoplasm and a neurofibrillary background (Fig. 13-31). Mitoses are usually rare,
but they may be seen in the small cell component. Necrosis
is rare in these tumors. Tumor cells may surround tubules of
the epididymis in an infiltrative pattern. Metastatic lesions
may contain either the larger, pigmented cells or the neuroblast-like cells, and ganglion cell differentiation has been
described in metastatic lesions.423,427
Melanotic neuroectodermal tumor of infancy expresses
epithelial, neural, and melanocytic immunohistochemical
markers. The pigmented cells stain for both cytokeratin and
HMB.45; they may also be EMA-positive. Both cell populations often stain positively with antibodies to neuron-specific
enolase and Leu7. The cells resembling neuroblasts stain
positively for glial fibrillary acidic protein, neurofilament
protein, and synaptophysin.428 Negative staining for desmin
excludes rhabdomyosarcoma and desmoplastic round cell
tumor from the differential diagnosis, but occasional melanotic tumors of infancy do display desmin positivity.425
Ultrastructural analysis shows both epithelial and melanocytic differentiation in the large cells, which contain desmosomes as well as melanosomes and pre-melanosomes.
The smaller, neuroblast-like cells contain dense-core granules and microtubules; they also form dendritic processes.425
Rare cells may contain both dense-core granules and
melanosomes.40
Recognition of the dual cell population in a paratesticular
tumor in a young infant is the key to the correct diagnosis. If
pigmented cells are scant or only one cell population is seen,
the differential diagnosis includes other small round blue cell
tumors. Thorough sampling to reveal both cell populations is
F i g u r e 1 3 - 3 1 n Melanotic
neuroectodermal
tumor
of
infancy. A: Low-power photograph showing infiltrating
mela­nocytic lesion involving epididymis. B: Note nests and cords
of epithelioid cells with abundant
melanin pigment.
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Chapter 13 n Pathology of the Paratesticular Region 843 essential. Positivity of the large cells for HMB45 excludes
the possibility of either rhabdomyosarcoma or desmoplastic
small round cell tumor. Homer-Wright rosettes characteristic of neuroblastoma are not seen in melanotic neuroectodermal tumor of infancy. A panel of immunostains is useful, but
the fact that melanotic neuroectodermal tumor of infancy
may be desmin-positive should be borne in mind.
Behavior of melanotic neuroectodermal tumors of
infancy is unpredictable. Recurrences may be seen in about
half of patients when all primary disease sites are considered, with metastatic disease occurring in 5% to 10% of
cases.427,428 Two of twenty-four patients with paratesticular
tumors have had local or regional lymph node metastases.
One patient was treated with chemotherapy and the other
with lymph node dissection; both were disease free after
24 and 48 months.423,427 There are no histologic criteria to
predict which tumors may recur or metastasize.
Desmoplastic Small Round Cell Tumor
F i g u r e 1 3 - 3 2 n Desmoplastic small round cell tumor. Note
sheets and broad trabeculae of poorly differentiated cohesive cells
separated by abundant fibrous stroma. (Image courtesy of Dr
Steven Shen, Houston, TX.)
Desmoplastic small round cell tumors are highly aggressive
small round blue cell tumors that arise in association with
mesothelial surfaces. They are much more common in males
than in females. They have a distinctive immunophenotype
and they are associated with a specific chromosomal abnormality. They metastasize and also spread by serosal seeding. Paratesticular desmoplastic small round cell tumors are
associated with the tunica vaginalis. They may be primary
or secondary. Several of these tumors have been reported in
patients who presented with symptoms in the paratesticular
region.429–433
These neoplasms occur in young patients between the
ages 17 and 35 years. Patients typically present with a painless scrotal mass that may be accompanied by swelling of
the scrotum and leg. Some patients have had symptoms for
only 1 month, whereas others report symptoms for 2 years
before diagnosis.432
Desmoplastic small round cell tumors are firm, graywhite neoplasms that may display areas of necrosis or myxoid change on gross examination. In the paratestis, these
tumors usually consist of a dominant nodule that measures
between 2.5 and 5.5 cm in diameter, with surrounding satellite nodules studding the testicular tunics and involving the
epididymis.40
Microscopic examination (Fig. 13-32) typically shows
fibrous stroma surrounding nests of tumor cells with
enlarged, hyperchromatic round nuclei, little cytoplasm,
numerous mitotic figures, and areas of necrosis. Cell borders are indistinct. Lymphovascular space invasion is often
present. However, atypical histologic features may complicate the diagnosis. Glands, pseudorosettes, signet ring cells,
and rhabdoid features may be present.434,435 Some tumors
have abundant eosinophilic cytoplasm that produces a rhabdoid appearance to the cells, some contain glycogen, and
some tumors have mucin-negative cytoplasmic vacuoles
that produce a signet ring appearance in the neoplastic cell
nests.434–436 Pseudorosettes and tubular formations mimic
the appearance of primitive neuroectodermal tumor in some
cases of desmoplastic small round cell tumor. Psammoma
bodies have been reported in one case of paratesticular desmoplastic small round cell tumor.430
Desmoplastic small round cell tumors have a very distinct,
polyphenotypic immunohistochemical profile. These neoplasms express three different intermediate filaments, including cytokeratin, desmin, and vimentin. Immunohistochemical
stains are useful in distinguishing these tumors from other
round cell sarcomas including rhabdomyosarcoma and
primitive neuroectodermal tumors.436 Desmoplastic round
cell tumors show positive staining for desmin, cytokeratin
(often with a dot-like pattern), epithelial membrane antigen,
neuron-specific enolase, vimentin, and often WT1. Some
tumors stain for MIC2.436 Stains for actin and chromogranin
are generally negative. Rare tumors with the characteristic
chromosomal translocation seen in desmoplastic small round
cell tumors have failed to express cytokeratin or epithelial
membrane antigen.437
Electron microscopy reveals nonspecific features that
include primitive cells with a few poorly developed cell
junctions, aggregates of intermediate filaments, some glycogen, and rare dense-core granules.437
Desmoplastic small round cell tumors display a unique
chromosomal abnormality, t(11;22) (p13,q12) that results
in the fusion of the EWS gene on chromosome 22 to
the Wilms tumor suppressor gene (WT1) on chromosome 11. The EWS-WT1 transcript can be detected by
reverse transcriptase–polymerase chain reaction or by
immunohistochemistry.437
The differential diagnosis of paratesticular desmoplastic
small round cell tumor includes embryonal rhabdomyosarcoma, lymphoma, primitive neuroectodermal tumor, and
melanotic neuroectodermal tumor of infancy. Paratesticular
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844 Urological Pathology
rhabdomyosarcoma most commonly occurs in children,
whereas desmoplastic small round cell tumor is usually seen
in young adults. Rhabdomyosarcomas stain with antibodies
to muscle-specific actin (HHF35), in contrast to desmoplastic small round cell tumor, which is negative for actin markers. Both tumors stain for desmin. Only desmoplastic small
round cell tumor is polyimmunophenotypic, with positive
staining to cytokeratin, epithelial membrane antigen, and
neuron-specific enolase in addition to desmin and vimentin.
Malignant lymphoma also displays a small round blue
cell population, but the cells are not arranged in the nested
aggregates seen in desmoplastic small round cell tumor.
Immunohistochemical profiles of these two neoplasms are
completely different and will resolve any diagnostic problems between the two tumors. As mentioned above, occasional desmoplastic small round cell tumors display tubules
and rosettes, leading to potential confusion with primitive
neuroectodermal tumor.430 Cytokeratin and desmin positivity are characteristic of desmoplastic small round cell tumor,
in contrast to the MIC2 (HBA71) positivity that is seen in
primitive neuroectodermal tumors. However, MIC2 may be
seen in some desmoplastic small round cell tumors, and we
have seen some desmin staining in primitive neuroectodermal tumors. Cytokeratin staining is not seen in primitive
neuroectodermal tumors. Cytogenetic testing should resolve
the dilemma in difficult cases.
Desmoplastic small round cell tumors are very aggressive
malignant neoplasms; most patients do not survive more than
2 years. Paratesticular tumors may be detected at an earlier
stage than abdominal tumors and therefore have a slightly
better prognosis. A few patients have been alive without
disease 2.5 to 3 years after diagnosis.432 Treatment includes
aggressive surgery and intensive multidrug chemotherapy.438
Extratesticular Germ Cell Tumors
Primary paratesticular germ cell tumors have been rarely
described.439,440 Concurrent or regressed testicular germ cell
tumors should be excluded before diagnosing a primary
germ cell tumor in the paratestis. Significant scarring and/or
the presence of intratubular germ cell neoplasia provide evidence for a regressed testicular germ cell tumor. The possibility of undescended testes should also be excluded because
they may be a source of inguinal germ cell tumors.
Extratesticular Sex Cord–Stromal Tumors
Extratesticular sex cord–stromal tumors have been described
in the paratestis,441,442 but they are very rare. Some may arise
from Leydig cells present in the spermatic cord or from incidental Sertoli cell nodules in the epididymis or rete testis.40
Fibromas of gonadal stromal origin occur in the testis, but
some are adjacent to the tunica albuginea and may be confused with fibromas originating from the testicular tunics.
Fibromas of gonadal stromal origin have stroma resembling
ovarian fibromas, in contrast to the more collagenous and
less cellular fibromas originating from the testicular tunics.
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Neuroblastoma
The paratestis has been a presenting location for neuroblastoma in some young infants.443–445 Some neuroblastomas
represent metastases from primary tumors in the adrenal
gland,443 but one paratesticular neuroblastoma associated
with ectopic adrenal cortical tissue was considered to represent multifocal origin of the tumor.444 These tumors are
small round blue cell tumors with a neurofibrillary background, often a high mitotic rate, and variable numbers of
­Homer-Wright pseudorosettes.
Paraganglioma
Six cases of paraganglioma have been reported in the spermatic cord.446 These lesions usually present as mass lesions
without neuropeptide production. These tumors display the
typical “zellballen” surrounded by a delicate vascular network as seen in paragangliomas in more typical locations.
Immunohistochemical markers such as CD56, chromogranin, and synaptophysin are useful in confirming a diagnosis of paraganglioma. All cases reported in the paratesticular
region have been benign tumors.40
Carcinoid Tumor
One case of primary carcinoid tumor of the epididymis has
been reported.447 Other rare carcinoid tumors of the paratesticular region have been metastatic, rarely as the first manifestation of carcinoid tumors of the small intestine.448
Wilms Tumor
Fifteen cases of inguinal and scrotal Wilms tumor have
been reported.449 Primary extrarenal Wilms tumor has been
reported in the paratestis in two young children44,450 and a
23-year-old man.40 These tumors present as mass lesions and
have the epithelial, blastema, and stromal components characteristic of Wilms tumor. The possibility of metastatic tumor
from the kidney should be excluded, although m
­ etanephric
rests in the paratesticular region could represent a precursor lesion. Primary extrarenal nephrogenic rests also occur
rarely in this anatomic region45 and must be distinguished
from Wilms tumor.
Squamous Cell Carcinoma
There is a single report of paratesticular squamous cell carcinoma in a hydrocele sac of an 85-year-old man.451 The
hydrocele sac displayed squamous metaplasia, dysplasia,
and invasive squamous carcinoma.
Secondary Neoplasms
Metastatic tumors may be seen in the epididymis, testicular
tunics, and the spermatic cord. In one review of 112 paratesticular tumors, 5 neoplasms represented tumor metastatic
to the paratesticular region.441 A different study found that
10/11/2013 11:43:51 AM
Chapter 13 n Pathology of the Paratesticular Region 845 prominent lymphatic or vascular space invasion by tumor,
signet ring cells, or architecture not typical of known tumors
of the paratesticular region should prompt consideration of
a metastatic lesion.
Since metastases in the paratesticular region are usually
associated with advanced disease, patients have a very poor
prognosis. The average survival after discovery of the metastatic tumor was 9.1 months in one series.452
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F i g u r e 1 3 - 3 3 n Metastatic prostatic carcinoma in rete testis.
Tumor present in lymphatic and vascular spaces is characteristic of
metastatic carcinoma.
metastatic tumors accounted for only 8.1% of all malignant
tumors of the epididymis and/or spermatic cord.452 Most
cancers that metastasize to the paratestis are known carcinomas in men over the age of 50 with high-stage disease, but
paratesticular metastases may rarely be the presenting finding. Metastatic tumors in the paratestis may present as fixed
inguinal hernias, intrascrotal masses, or areas of thickening
of the spermatic cord. Some metastatic tumors are discovered incidentally.
Stomach cancer has been the most frequent type of
metastatic tumor in the spermatic cord and epididymis; it
accounts for 42.8% of metastases to these sites.452 Prostate
cancer accounts for 28.5% of metastases (Fig. 13-33).452
Other primary tumor sites include the testis, kidney,453 lung,
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Other neoplasms metastasize by way of lymphatic and vascular channels. There may be a tendency for left-sided renal
cell carcinoma to metastasize to the paratesticular region
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region includes adenocarcinoma of the epididymis, rete testis adenocarcinoma, primary serous carcinoma of the paratesticular region, and malignant mesothelioma. Evaluation
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renal cell carcinoma both occur in patients with von HippelLindau syndrome, but the bland cytologic features and cystic
spaces seen in cystadenoma are helpful for that diagnosis. In
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